"Descrizione" about Covid-19 history, defenses, therapies Review Consensus 10 by Al222 (17613 pt) | 2021-Apr-07 12:45 |
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Coronaviruses, a name coined in 1968 derived from the crown morphology of its structure, are a group of viruses that affect the respiratory tract. Coronavirus COVID-19 spreads predominantly through the respiratory tract with a high degree of infectivity. They belong to the subfamily Coronavirinae which together with Torovirinae form the family Coronaviridae in the order Nidovirales and are known to infect mammals and birds. Genotypically, coronaviruses can be divided into three groups. Group III viruses are found exclusively in birds, while group I and II viruses have mammals as their hosts (1).
Coronaviruses belong to the subfamily Coronavirinae that together with Torovirinae form the family Coronaviridae in the order Nidovirales (2) created in 1996.
Infection and Mortality
Influenza epidemics result in increased mortality due both to influenza itself and pneumonia, but also from complications and exacerbation of other chronic diseases due to influenza. In the absence of laboratory tests, it is not easy to determine whether deaths are attributable to influenza as a primary cause.
Between 250,000 and 500,000 influenza-associated deaths occur each year, according to WHO estimates (3)
The 1918/1919 pandemic influenza so-called Spanish flu (H1N1 strain), developed in a three-wave pattern and caused the deaths of approximately 50 million people (4) with a mortality rate, worldwide, of 2-3%. Although criticized, one study (5) believed that there were phylogenetic similarities between Spagnola and coronavirus. Age groups most infected: young adults.
The first coronavirus was discovered in 1930 (6).
The second coronavirus, in the years 1957-1958 ( HCoV-229E and HCoV-OC43) or so-called Asian influenza (strain H2N2), of presumably avian origin, developed in February in Guizhou province in southern China, spread in March to Hunan province, in April to Singapore and Hong Kong, in a two-wave pattern caused the death of about 1/4 million people worldwide with a mortality rate of 0.2%. Most infected age groups: all age groups (7).
The third coronavirus in 1968 or Hong Kong influenza (strain H3N2), presumably of avian origin, caused the death of about 1 million people with a similar mortality rate as in 1957 of 0.2%. Age groups most infected: all age groups (6).
In November 2002, SARS-CoV developed in Foshan, Guangdong Province, mainland China, with a new coronavirus, the fourth, as the causative agent. The origin appears to be from two animals: civet (Paguma larvata) and raccoon (Nyctereutes procynonoides), which are sold in markets as culinary delicacies. SARS-CoV has infected more than 8000 people and caused 774 deaths in 26 countries on five continents. Age groups most infected: all age groups (8).
In June 2009, a coronavirus, the fifth, resulting from the combination of genetic segments of avian, swine, and human influenza viruses originating in Mexico (H1N1pdm09) killed an estimated 200-400,000 people worldwide with a mortality rate of 0.02%. Age groups most infected: children and adults. The pandemic was officially declared over by the WHO in August 2010. This influenza has shown an anomalous figure compared to similar seasonal epidemics: about 80% of deaths have affected people under 65 years of age, while an estimated 80-90% of deaths caused by previous seasonal epidemics have been in the older population, 65 years and over (9).
In April 2020 COVID-19 (developed in Wuhan, China) infected nearly 3 million people and caused the death of more than 200,000 people with a 6.7% mortality rate
Coronavirus COVID-19 developed in China from two strains of different animal origin: bat and pangolin (10) although other studies consider COVID-19 closely related to coronaviruses derived from wild animals, including Paguma larvata, Paradoxurus hermaphroditus, Civet, Aselliscus stoliczkanus, and Rhinolophus sinicus, located in the same branch of the phylogenetic tree. However, genome and ORF1a homology show that the virus is not the same coronavirus as that derived from these animals, whereas the virus has the highest homology with the isolated bat coronavirus RaTG13. On the pangolin, genome affinity is still unclear (11).
Some evidence, however, suggests that it may have come from laboratories. In fact, in September 2003 in Singapore, China, there was an episode of Coronavirus SARS. The patient, with overt SARS symptoms, was working in a laboratory and had reported working on West Nile virus, but the laboratory was doing live SARS work at the time (12).
Droplet transmission is the primary route (13), and travel was the main source of transmission of COVID-19 cases during the early stages of the current outbreak in Italy (14) and China. This study found that 779 cases would have been exported from China by February 15, 2020, because of the lack of border restrictions or travel restrictions and that travel-blocking measures implemented by the Chinese government subsequently prevented 70.5% of infections (15). Notably, the coincidence of the Spring Festival in China increased travel volumes from Wuhan, Hubei province, the epicenter of COVID-19 spreading the epidemic (16).
Defenses
COVID-19 enters the human body primarily through exposure to respiratory droplet clouds that expand approximately 5 meters or more caused by sneezing or coughing from infected persons. These clouds can travel through the air, and at least 20% can remain alive for 3 hours to 6 days (17).
Currently, the only defense available, vaccines aside, is the maintenance of distance between individuals and respiratory protection devices that are used by those who must defend themselves from radioactive materials, biological, chemical.
Half-face respirators are easy to wear and lightweight. There are currently several types of these respirators on the market, which are classified in Europe (EN 149:2001) as FFP1 (minimum filtration efficiency 80%), FFP2 (minimum filtration efficiency 94%) and FFP3 (minimum filtration efficiency 99%), while the US National Institute for Occupational Safety and Health (NIOSH) classifies them as N95 (minimum filtration efficiency 95%), N99 (minimum filtration efficiency 99%), N100 (minimum filtration efficiency 99.97%) (18). Surgical masks commonly used by physicians in the operating room are also on the market.
Studies have verified the effective protection of these respirators.
Influenza and coronavirus viruses are particle sizes ranging from 0.04 to 0.2 um.
This 2008 study concludes that the N95 respirators tested had provided about 8-12 times better protection than surgical masks. However, approximately 29% of the N95 respirators tested had a PF of less than 10, indicating that the PF 10 value established by the US Occupational Safety and Health Administration (OSHA) overestimates the actual protection offered by N95 respirators against bacteria and viruses. N95 filtering-mask respirators with valves demonstrated nearly equal protection to those without valves against bacterial and viral particles (19).
In a more recent study from 2016, laboratory tests showed that 10% of FFP2 respirators and 28.2% of FFP3 respirators had lower protection factors than those assigned by the European standard EN 149:2001 (20).
The search for therapy
Monoclonal antibodies represent the main class of biotherapeutics for passive immunotherapy to fight viral infections (21). However, they have contraindications that must be evaluated on a case-by-case basis. Tocilizumab (distributed free of charge by Roche while supplies last), can help patients breathe independently and get out of the ICU.
A temporary suggestion probably resistant to new coronavirus mutations is the use of angiotensin type 1 receptor blockers as therapeutics to reduce aggressiveness and mortality from SARS-CoV-2 virus infections (22).
Nucleoside analogs such as favipiravir (T-705 or 6-fluoro-3-oxo-3,4-dihydropyrazine-2-carboxamide) approved for new strains that do not respond to current antivirals, marketed and approved in Japan under the name Avigan®, as well as ribavirin (Tribavirin or Virazole) and experimental nucleoside analogs such as remdesivir (a nucleotide analog formulation currently in clinical trials for the treatment of Ebola virus infections) and galidesivir, may have potential on 2019-nCoV (23) but remdesivir appeared superior in efficacy to lopinavir/ritonavir and interferon beta against MERS-CoV in a model of humanized transgenic mice (24). Regarding efficacy, favipiravir demonstrated an IC50 (concentration required to inhibit 50% of the target) of 601 μM versus 3.9 μM attributed to ribavirin (25), but its use is approved with limitations because it has a risk of teratogenicity and hemotoxicity (26).
This study describes the first generation of MERS-CoV fusion inhibitors with potencies in the low micromolar range (27).
Chloroquine phosphate, a drug already effective in the treatment of malaria, has been shown to have apparent efficacy and acceptable safety against COVID-19-associated pneumonia in multicenter clinical trials conducted in China (28) in 500mg tablets twice daily for 10 days to patients diagnosed as mild cases, moderate and severe cases of new coronavirus pneumonia and without contraindications to chloroquine (29) and already proposed 20 years ago by the authors of this study as effective in vitro against a wide range of viruses (30), while another study considers hydroxychloroquine more potent and more tolerable (31).
Procalcitonin, a prohormone precursor to calcitonin, a diagnostic biomarker approved by the FDA in 2005, for patients with more severe symptoms of Coronavirus 2019 (COVID-19)(32) in the ICU.
In in vitro experiments, the alkaloid cepharanthine, selamectin, and mefloquine hydrochloride, another known remedy for malaria, were effective against pangolin-originated coronavirus (33).
During the severe COVID-19 outbreak, many hospitals administered Tocilizumab in intubated patients who were able to breathe on their own thanks to this monoclonal antibody.
People of advanced age are more likely to experience acute respiratory distress syndrome (ARDS), and this study suggests treatment with methylprednisolone (34), a synthetic glucocorticoid and potent anti-inflammatory.
A highly standardized mixture of active compounds derived from the action of Lentinula Edodes Mycelia (AHCC) that can promote a protective response to a wide range of viral infections, and the current absence of effective vaccines could support its use in the prevention of diseases caused by human pathogenic coronaviruses, including COVID-19 (35).
It is important to understand the defense dynamics of coronavirus to try to inhibit its replication, a very complex process aimed at preserving its large RNA genome. Replication and maturation of the virus have essential strengths in several proteases including Mpro or 3CL and the papain-like protease (PLpro) capable of generating developed proteins.
In previous MERS-CoV and SARS-CoV, disulfiram (Tetraethylthiuram disulfide, Antabuse™) was shown to inhibit papain protease and act as an allosteric inhibitor for MERS-CoV and as a competitive (or mixed) inhibitor of SARS-CoV (36). However, it should not be coadministered with lopinavir/ritonavir (37).
In fact, PLpro plays a key role in virus defense because first and foremost it is responsible for shaking off host cell proteins that seek, through the immune response, to neutralize the virus (38) and also has a pharmacokinetic interaction on stimulating host interferon through its deubiquitination activity (39).
Disulfiram is a well-known remedy for alcoholism, but has also recently demonstrated efficacy against cancer, leukemia, and, importantly, low toxicity (40). This study showed that the disulfiram/copper complex significantly induced cell cycle arrest in the G2/M phase in MM.1S and RPMI8226 cells (41).
Between 2005 and 2009, several studies had identified 6-mercaptopurine (a US Food and Drug Administration (FDA)-approved anticancer drug) , 6-thioguanine (a chemotherapeutic drug), and mycophenolic acid as compounds capable of inhibiting PLpro of MERS-CoV through their synergistic effects and capable of forming a basis for antiviral drugs (42) (43).
In 2018, 6-thioguanine was suggested as a noncompetitive inhibitor of PLpro during the PEDV swine epidemic (44).
Another anti-infectious antimalarial drug, mefloquine, which is structurally related to quinine and is often combined with artesunate (a semisynthetic derivative of artemisinin) could provide results in combating coronavirus, but has contraindications due to both the long treatment period and potential side effects (45).
References_________________________________________________________________________
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"Descrizione" about Coronavirus and Covid-19 Review Consensus 10 by Al222 (17613 pt) | 2020-May-17 18:45 |
Read the full Tiiip | (Send your comment) |
Introduction
Coronaviruses, a name coined in 1968 that derives from the crown morphology of its structure, are a group of viruses that affect the respiratory tract. Coronavirus COVID-19 spreads predominantly through the respiratory tract with a high degree of infectivity. They belong to the subfamily Coronavirinae which together with Torovirinae form the family Coronaviridae in the order Nidovirales and are known to infect mammals and birds. Genotipically, coronaviruses can be divided into three groups. Group III viruses are found exclusively in birds, while Group I and II viruses have mammals as their host (1).
Coronaviruses belong to the subfamily Coronavirinae which together with Torovirinae form the family Coronaviridae in the order Nidovirales (2) created in 1996.
Infection and Mortality
Influenza epidemics lead to increased mortality due both to influenza itself and pneumonia, but also to complications and aggravation of other chronic illnesses due to influenza. In the absence of laboratory tests, it is not easy to determine whether the causes of deaths can be attributed to influenza as the primary cause.
Between 250,000 and 500,000 influenza-related deaths occur each year, according to WHO estimates (3).
The pandemic influenza pandemic of 1918/1919 so-called Spanish (H1N1 strain), developed with a three-wave model and caused the deaths of about 50 million people (4) with a worldwide mortality rate of 2-3%. Although criticized, one study (5) believed that there were phylogenetic similarities between Spanish and coronavirus. Most infected age groups: Young adults
The first coronavirus was discovered in 1930 (6).
The second coronavirus, in the years 1957-1958 ( HCoV-229E and HCoV-OC43) or so-called Asian influenza (strain H2N2), of presumably avian origin, developed in February in Guizhou province in southern China, spread in March in Hunan province, in April in Singapore and Hong Kong, in a two-wave model caused the death of about 1/4 million people worldwide with a mortality rate of 0.2%. Most infected age groups: all age groups (7).
The third coronavirus in 1968 or Hong Kong flu (H3N2 strain), presumably of avian origin, caused the deaths of about 1 million people with a mortality rate similar to 1957 of 0.2%. Most infected age groups: all age groups (6).
In November 2002 in Foshan, Guangdong Province, mainland China, SARS-CoV developed in Foshan, which had a new coronavirus, the fourth causative agent. The origin appears to come from two animals: civet (Paguma larvata) and raccoon (Nyctereutes procynonoides), sold in markets as culinary delicacies. SARS-CoV infected more than 8000 people and caused 774 deaths in 26 countries on five continents. Most infected age groups: all age groups (8).
In June 2009, a coronavirus, the fifth, resulting from a combination of genetic segments of avian, porcine and human influenza viruses originating in Mexico (H1N1pdm09) caused the deaths of about 200-400,000 people worldwide with a mortality rate of 0.02%. Most infected age groups: children and adults. The pandemic was declared officially over by the WHO in August 2010. This influenza showed an anomalous figure compared to similar seasonal epidemics: about 80% of deaths affected people under 65 years of age, while an estimated 80-90% of deaths caused by previous seasonal epidemics in the older population aged 65 and over (9).
In April 2020 COVID-19 (developed in Wuhan, China) infected nearly 3 million people and caused the death of more than 200,000 people with a mortality rate of 6.7%.
Coronavirus COVID-19 developed in China from two strains of different animal origin: bat and pangolin (10) although other studies believe COVID-19 is closely related to coronaviruses derived from wild animals, including Paguma larvata, Paradoxurus hermaphroditus, Civet, Aselliscus stoliczkanus and Rhinolophus sinicus, located in the same branch of the phylogenetic tree. However, the genome and ORF1a homology show that the virus is not the same coronavirus as that derived from these animals, while the virus has the highest homology with the bat coronavirus isolated RaTG13. On pangolin the genome affinity is not yet clear (11).
Some evidence, however, indicates that it could come from laboratories. In fact, an episode of Coronavirus SARS occurred in September 2003 in Singapore, China. The patient, with confirmed symptoms of SARS, was working in a laboratory and reported working on West Nile virus, but the laboratory was doing live SARS work at the time (12).
Droplet transmission is the main route (13) and travel was the main source of transmission of COVID-19 cases during the early stages of the current epidemic in Italy (14) and China. This study found that 779 cases would have been exported from China by 15 February 2020 due to the lack of border restrictions or travel restrictions and that the travel blocking measures applied by the Chinese government subsequently avoided 70.5 % of contagion (15). In particular, the coincidence of the Spring Festival in China increased travel volumes from Wuhan, Hubei Province, epicentre of COVID-19 spreading the epidemic (16).
The defenses
Since no vaccine or drug has been approved to date, the population remains defenceless from COVID-19 entering the human body mainly due to exposure to clouds of respiratory droplets expanding about 5 meters or more, caused by sneezing or coughing from infected people. These clouds can travel in the air and at least 20% can stay alive from 3 hours to 6 days (17).
Currently, the only defence available is to maintain the distance between individuals and respiratory protection devices that are used by those who have to defend themselves against radioactive, biological, chemical materials.
Half face respirators are easy to wear and lightweight. There are currently several types of these respirators on the market which are classified in Europe (EN 149:2001) as FFP1 (minimum filtration efficiency 80%), FFP2 (minimum filtration efficiency 94%) and FFP3 (minimum filtration efficiency 99%), while the US National Institute for Occupational Safety and Health (NIOSH) classifies them as N95 (minimum filtration efficiency 95%), N99 (minimum filtration efficiency 99%), N100 (minimum filtration efficiency 99.97%) (18). Surgical masks commonly used by doctors in the operating room are also available on the market.
Some studies have verified the effective protection of these respirators.
Influenza viruses and coronavirus are particles between 0.04 and 0.2 um.
This 2008 study concludes that the N95 respirators tested provided about 8-12 times better protection than surgical masks. However, approximately 29% of the N95 respirators tested had a PF of less than 10, indicating that the PF 10 value established by the US Occupational Safety and Health Administration (OSHA) overestimates the effective protection provided by N95 respirators against bacteria and viruses. The N95 filter mask respirators with valves showed almost the same protection against bacterial and viral particles as those without valves (19).
In a more recent study in 2016, laboratory tests showed that 10% of FFP2 respirators and 28.2% of FFP3 respirators had lower protection factors than those assigned by the European standard EN 149:2001 (20).
The search for therapy
No vaccine or drug has been approved to date
Monoclonal antibodies represent the main class of biotherapy for passive immunotherapy to combat viral infections (21). However, they have contraindications that should be evaluated on a case-by-case basis. Tocilizumab (distributed free of charge by Roche while stocks last) can help the patient to breathe independently and leave the intensive care unit.
A temporary suggestion, probably resistant to new coronavirus mutations, is the use of angiotensin type 1 receptor blockers as a therapy to reduce aggressiveness and mortality from SARS-CoV-2 infections (22).
Nucleoside analogs such as favipiravir (T-705 or 6-fluoro-3-oxo-3,4-dihydropyrazine-2-carboxamide) approved for new strains that do not respond to current antivirals, marketed and approved in Japan under the name Avigan®, as well as ribavirin (Tribavirin or Virazole) and experimental nucleoside analogues such as remdesivir (a nucleotide-like formula currently in clinical trials for the treatment of Ebola virus infections) and galidesivir, may have potential on 2019-nCoV (23) but remdesivir appeared superior in efficacy to lopinavir/ritonavir and interferon beta against MERS-CoV in a model of humanized transgenic mice (24). Regarding efficacy, favipiravir demonstrated an IC50 (concentration required to inhibit 50% of the target) of 601 μM versus 3.9 μM attributed to ribavirin (25), but its use is approved with limitations as it has a risk of teratogenicity and embotoxicity (26).
This study describes the first generation of MERS-CoV fusion inhibitors with potencies in the low micromolar range (27).
Chloroquine phosphate, an already effective drug for the treatment of malaria, has been shown to have apparent efficacy and acceptable safety against COVID-19 associated pneumonia in multicentre clinical trials conducted in China (28) in 500mg tablets twice daily for 10 days in patients diagnosed as mild cases, moderate and severe new coronavirus-related pneumonia without contraindications to chloroquine (29) and already proposed 20 years ago by the authors of this study as effective in vitro against a wide range of viruses (30), while another study considers hydroxychloroquine more potent and more tolerable (31).
Procalcitonin, a prohormone precursor of calcitonin, a diagnostic biomarker approved by the FDA in 2005, for patients with more severe symptoms of Coronavirus 2019 (COVID-19)(32) in intensive care.
In in vitro experiments have been found to be effective against pangolin-borne coronavirus, cepharanthin alkaloid, selamectin, and mefloquine hydrochloride, another known remedy against malaria (33).
During the severe COVID-19 epidemic, many hospitals administered Tocilizumab to intubated patients who were able to breathe independently thanks to this monoclonal antibody.
People in old age are more likely to contract acute respiratory distress syndrome (ARDS) and this study suggests treatment with methylprednisolone (34), synthetic glucocorticoid and potent anti-inflammatory drug.
A highly standardized blend of active compounds derived from the action of Lentinula Edodes Mycelia (AHCC) that can promote a protective response to a wide range of viral infections, and the current absence of effective vaccines could support its use in the prevention of diseases caused by human pathogenic coronaviruses, including COVID-19 (35).
It is important to understand the defence dynamics of coronavirus to try to inhibit its replication, a very complex process aimed at preserving its large RNA genome. Replication and maturation of the virus have essential strengths in several proteases including Mpro or 3CL and papain-like protease (PLpro) capable of generating developed proteins.
In previous MERS-CoV and SARS-CoV disulfiram (Tetraethylthiuram disulfide, Antabuse™) had been shown to inhibit papain protease and act as an allosteric inhibitor for MERS-CoV and as a competitive (or mixed) SARS-CoV inhibitor (36). However, it should not be co-administered to lopinavir/ritonavir (37).
In fact, PLpro plays a fundamental role in the defense of the virus as it is primarily responsible for shaking off the proteins of host cells that try, with the immune response, to neutralize the virus (38) and also plays a pharmacokinetic interaction on the stimulation of the host interferon through its deubiquitination activity (39).
Disulfiram is a well known remedy against alcoholism, but it has also recently demonstrated its effectiveness against cancer, leukemia and, importantly, low toxicity (40). This study showed that the disulfiram/copper complex significantly induced the arrest of the cell cycle in the G2/M phase in MM.1S and RPMI8226 cells (41).
Between 2005 and 2009 some studies had identified 6-mercaptopurins (an antitumor drug approved by the US Food and Drug Administration (FDA)), 6-thioguanins (a chemotherapeutic drug) and mycophenolic acid as compounds able to inhibit PLpro of MERS-CoV through their synergistic effects and able to constitute a basis for antiviral drugs (42) (43).
In 2018, during the PEDV pig epidemic, 6-thioguanine was suggested as a non-competitive PLpro inhibitor (44).
Another anti-malarial anti-infective drug, mefloquine, structurally related to quinine, which is often combined with artesunate (a semi-synthetic derivative of artemisininin) could provide results in the fight against coronavirus, but has contraindications both for the long treatment period and for potential side effects (45).
References_________________________________________________________________________
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(8) Joseph S.M. Peiris, M.D., D.Phil., Kwok Y. Yuen, M.D., Albert D.M.E. Osterhaus, Ph.D., and Klaus Stöhr, Ph.D. The Severe Acute Respiratory Syndrome December 18, 2003 N Engl J Med 2003; 349:2431-2441 DOI: 10.1056/NEJMra032498
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(10) Fan HH, Wang LQ, Liu WL, An XP, Liu ZD, He XQ, Song LH, Tong YG. Repurposing of clinically approved drugs for treatment of coronavirus disease 2019 in a 2019-novel coronavirus (2019-nCoV) related coronavirus model. Chin Med J (Engl). 2020 Mar 6. doi: 10.1097/CM9.0000000000000797.
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(14) Porcheddu R, Serra C, Kelvin D, Kelvin N, Rubino S. Similarity in Case Fatality Rates (CFR) of COVID-19/SARS-COV-2 in Italy and China. J Infect Dev Ctries. 2020 Feb 29;14(2):125-128. doi: 10.3855/jidc.12600.
(15) Wells CR, Sah P, Moghadas SM, et al. Impact of international travel and border control measures on the global spread of the novel 2019 coronavirus outbreak [published online ahead of print, 2020 Mar 13]. Proc Natl Acad Sci U S A. 2020;202002616. doi:10.1073/pnas.2002616117
(16) Zhong P, Guo S, Chen T. Correlation between travellers departing from Wuhan before the Spring Festival and subsequent spread of COVID-19 to all provinces in China [published online ahead of print, 2020 Mar 17]. J Travel Med. 2020;taaa036. doi:10.1093/jtm/taaa036
(17) Ijaz MK, Brunner AH, Sattar SA, Nair RC, Johnson-Lussenburg CM. Survival characteristics of airborne human coronavirus 229E. J Gen Virol. 1985;66 ( Pt 12):2743–2748. doi:10.1099/0022-1317-66-12-2743
(18) National Institute for Occupational Safety and Hygiene (NIOSH) NIOSH Guide to the Selection and Use of Particulate Respirators Certified Under 42 CFR 84. Cincinnati, Ohio, USA: National Institute for Occupational Safety and Hygiene (NIOSH); 1996
(19) Lee SA, Grinshpun SA, Reponen T. Respiratory performance offered by N95 respirators and surgical masks: human subject evaluation with NaCl aerosol representing bacterial and viral particle size range. Ann Occup Hyg. 2008;52(3):177–185. doi:10.1093/annhyg/men005
(20) Lee SA, Hwang DC, Li HY, Tsai CF, Chen CW, Chen JK. Particle Size-Selective Assessment of Protection of European Standard FFP Respirators and Surgical Masks against Particles-Tested with Human Subjects. J Healthc Eng. 2016;2016:8572493. doi:10.1155/2016/8572493
(21) Shanmugaraj B, Siriwattananon K, Wangkanont K, Phoolcharoen W.Perspectives on monoclonal antibody therapy as potential therapeutic intervention for Coronavirus disease-19 (COVID-19). Asian Pac J Allergy Immunol. 2020 Mar 4. doi: 10.12932/AP-200220-0773.
(22) Gurwitz D. Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics. Drug Dev Res. 2020 Mar 4. doi: 10.1002/ddr.21656.
(23) Li G, De Clercq E. Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nat Rev Drug Discov. 2020 Mar;19(3):149-150. doi: 10.1038/d41573-020-00016-0.
Dong L, Hu S, Gao J. Discovering drugs to treat coronavirus disease 2019 (COVID-19). Drug Discov Ther. 2020;14(1):58-60. doi: 10.5582/ddt.2020.01012.
(24) Martinez MA. Compounds with therapeutic potential against novel respiratory 2019 coronavirus. Antimicrob Agents Chemother. 2020 Mar 9. pii: AAC.00399-20. doi: 10.1128/AAC.00399-20.
(25) Furuta Y, Gowen BB, Takahashi K, Shiraki K, Smee DF, Barnard DL. Favipiravir (T-705), a novel viral RNA polymerase inhibitor. Antiviral Res. 2013 Nov;100(2):446-54. doi: 10.1016/j.antiviral.2013.09.015.
(26) Nagata T, Lefor AK, Hasegawa M, Ishii M. Favipiravir: a new medication for the Ebola virus disease pandemic. Disaster Med Public Health Prep. 2015;9(1):79–81. doi:10.1017/dmp.2014.151
(27) Kandeel M, Yamamoto M, Al-Taher A, Watanabe A, Oh-Hashi K, Park BK, Kwon HJ, Inoue JI, Al-Nazawi M. Small Molecule Inhibitors of Middle East Respiratory Syndrome Coronavirus Fusion by Targeting Cavities on Heptad Repeat Trimers. Biomol Ther (Seoul). 2020 Mar 4. doi: 10.4062/biomolther.2019.202.
(28) Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends. 2020 Feb 19. doi: 10.5582/bst.2020.01047.
(29) Zhonghua Jie He He Hu Xi Za Zhi. multicenter collaboration group of Department of Science and Technology of Guangdong Province and Health Commission of Guangdong Province for chloroquine in the treatment of novel coronavirus pneumonia. Expert Consensus on Chloroquine Phosphate for the Treatment of Novel Coronavirus Pneumonia 2020;43(3):185–188. doi:10.3760/cma.j.issn.1001-0939.2020.03.009
(30) Colson P, Rolain JM, Raoult D. Chloroquine for the 2019 novel coronavirus SARS-CoV-2. Int J Antimicrob Agents. 2020 Feb 15:105923. doi: 10.1016/j.ijantimicag.2020.105923.
(31) Yao X, Ye F, Zhang M, Cui C, Huang B, Niu P, Liu X, Zhao L, Dong E, Song C, Zhan S, Lu R, Li H, Tan W, Liu D. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020 Mar 9. pii: ciaa237. doi: 10.1093/cid/ciaa237.
(32) Lippi G, Plebani M. Procalcitonin in patients with severe coronavirus disease 2019 (COVID-19): a meta-analysis. Clin Chim Acta. 2020 Mar 4. pii: S0009-8981(20)30106-6. doi: 10.1016/j.cca.2020.03.004.
Chanu Rhee, Using Procalcitonin to Guide Antibiotic Therapy, Open Forum Infectious Diseases, Volume 4, Issue 1, Winter 2017, ofw249, https://doi.org/10.1093/ofid/ofw249
(33) Fan HH, Wang LQ, Liu WL, An XP, Liu ZD, He XQ, Song LH, Tong YG. Repurposing of clinically approved drugs for treatment of coronavirus disease 2019 in a 2019-novel coronavirus (2019-nCoV) related coronavirus model. Chin Med J (Engl). 2020 Mar 6. doi: 10.1097/CM9.0000000000000797.
(34) Wu C, Chen X, Cai Y, et al. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China [published online ahead of print, 2020 Mar 13]. JAMA Intern Med. 2020;10.1001/jamainternmed.2020.0994. doi:10.1001/jamainternmed.2020.0994
(35) Di Pierro F, Bertuccioli A, Cavecchia I. Possible therapeutic role of a highly standardized mixture of active compounds derived from cultured Lentinula edodes mycelia (AHCC) in patients infected with 2019 novel coronavirus [published online ahead of print, 2020 Mar 12]. Minerva Gastroenterol Dietol. 2020;10.23736/S1121-421X.20.02697-5. doi:10.23736/S1121-421X.20.02697-5
(36) Lin MH, Moses DC, Hsieh CH, et al. Disulfiram can inhibit MERS and SARS coronavirus papain-like proteases via different modes. Antiviral Res. 2018;150:155–163. doi:10.1016/j.antiviral.2017.12.015
(37) Cvetkovic RS, Goa KL. Lopinavir/ritonavir: a review of its use in the management of HIV infection. Drugs. 2003;63(8):769–802. doi:10.2165/00003495-200363080-00004
(38) Brian DA, Baric RS. Coronavirus genome structure and replication. Curr Top Microbiol Immunol. 2005;287:1-30.
(39) Báez-Santos YM, St John SE, Mesecar AD. The SARS-coronavirus papain-like protease: structure, function and inhibition by designed antiviral compounds. Antiviral Res. 2015 Mar;115:21-38. doi: 10.1016/j.antiviral.2014.12.015.
(40) Sheppard JG, Frazier KR, Saralkar P, Hossain MF, Geldenhuys WJ, Long TE. Disulfiram-based disulfides as narrow-spectrum antibacterial agents. Bioorg Med Chem Lett. 2018;28(8):1298–1302. doi:10.1016/j.bmcl.2018.03.023
(41) Xu Y, Zhou Q, Feng X, et al. Disulfiram/copper markedly induced myeloma cell apoptosis through activation of JNK and intrinsic and extrinsic apoptosis pathways [published online ahead of print, 2020 Mar 4]. Biomed Pharmacother. 2020;126:110048. doi:10.1016/j.biopha.2020.110048
(42) Cheng KW, Cheng SC, Chen WY, et al. Thiopurine analogs and mycophenolic acid synergistically inhibit the papain-like protease of Middle East respiratory syndrome coronavirus. Antiviral Res. 2015;115:9–16. doi:10.1016/j.antiviral.2014.12.011
(43) Chou CY, Chien CH, Han YS, et al. Thiopurine analogues inhibit papain-like protease of severe acute respiratory syndrome coronavirus. Biochem Pharmacol 2008;75:1601–1609.
(44) Chu HF, Chen CC, Moses DC, et al. Porcine epidemic diarrhea virus papain-like protease 2 can be noncompetitively inhibited by 6-thioguanine. Antiviral Res. 2018;158:199–205. doi:10.1016/j.antiviral.2018.08.011
(45) Nevin RL, Byrd AM. Neuropsychiatric Adverse Reactions to Mefloquine: a Systematic Comparison of Prescribing and Patient Safety Guidance in the US, UK, Ireland, Australia, New Zealand, and Canada. Neurol Ther. 2016;5(1):69–83. doi:10.1007/s40120-016-0045-5
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"Descrizione" about Coronavirus COVID-19 Trend 30/3/2020 Review Consensus 9 by Al222 (17613 pt) | 2020-Mar-28 12:15 |
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To better interpret the data and trend of Coronavirus COVID-19.
Day-to-day data provides an immediate view whose interpretation, in my opinion, can generate misleading predictions. I have analyzed the situation with the data every 5/7 days and the result seems more understandable to me.
Of all the graphs and methods I have used so far, the ones that follow and in particular the second and third ones give me more confidence in a decrease of contagion within 3/4 weeks.
The first two graphs concern Turin and Milan from 8/3/2020 to 26/3/2020. where it is observed that the trend has repeated wave oscillations every 5/7 days.
First graph: Percentage of increase in contagion on the previous day compared to the city's population. Turin and Milan.
The growth line is unequivocal, but let's look at the other graphs.
Second graph: Percentage of infected people of the day compared to the population of the city. Turin and Milan.
Surprise. The graph is very different and indicates that the trend has repeated wave oscillations every 5/7 days.
We now see a graph that, in addition to Turin and Milan, includes the most affected city, Bergamo.
Third graph: Percentage of infected people of the day compared to the population of the city. Turin, Milan and Bergamo.
Also a surprise here. We have 3 waves with a fairly similar trend and it seems that the last one is losing strength.
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"Descrizione" about Coronavirus COVID-19 . What destroys the Coronavirus? Review Consensus 8 by Al222 (17613 pt) | 2020-Mar-24 11:14 |
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The coronavirus remains infectious on the pulmonary surfaces for about 5 days and on inanimate surfaces for a few hours, but this is enough time to cause one or more infections.
An efficient disinfection process should start from the well-known concept that only what is clean can be disinfected efficiently. with alcohol-based disinfectants (1).
However, it has been shown that the type HCoV-229E, a coronavirus belonging to the alphacoronavirus (α-CoV) family and identified in 1996 (2), but rather similar to COVID-19, behaves differently depending on the surface on which it is placed.
Rapid deactivation, irreversible destruction of viral RNA and massive structural damage in coronavirus exposed to copper and copper alloy surfaces has been confirmed (3).
After exposure to the surfaces of two metal catalysts Ag/Al2O3 and Cu/Al2O3 for 5 and 20 min, SARS-CoV infectivity in Vero cells and baculovirus in Sf9 cells dropped to a very low and undetectable level, and no colony was detected using the bacterial culture method (4).
After exposure to the surfaces of two metal catalysts Ag/Al2O3 and Cu/Al2O3 for 5 and 20 min, SARS-CoV infectivity in Vero cells and baculovirus in Sf9 cells dropped to a very low and undetectable level, and no colony was detected using the bacterial culture method (4).
It was found, using a coronavirus strain of SARS CoV-P9, that the viruses maintained their stability at 37 degrees C for at least 2 hours without significant change in the infectious capacity of the cells, but became non-infectious after 90 minutes exposure at 56 degrees C. UV irradiation of the virus for 60 minutes effectively eliminated viral infectivity (5).
Other studies have observed preventive coronavirus antiviral and contrast activity using silver-graphene nanocomposites (6), silver nanomaterials (7).
The temperature is important. In experiments on copper surfaces, cells have survived much longer on copper alloys at a temperature of 4 degrees centigrade than at a temperature of 21 degrees centigrade (8) and this should also apply to other surfaces such as copper alloys and silver alloys.
The temperature is important. In experiments on copper surfaces, cells have survived much longer on copper alloys at a temperature of 4 degrees centigrade than at a temperature of 21 degrees centigrade (8). In addition, higher humidity improves the effectiveness of antibacterial activity (9). This last two considerations also apply to other surfaces such as copper alloys and silver alloys.
References________________________________________
(1) Geller C, Varbanov M, Duval RE. Human coronaviruses: insights into environmental resistance and its influence on the development of new antiseptic strategies. Viruses. 2012;4(11):3044–3068. Published 2012 Nov 12. doi:10.3390/v4113044
(2)Hamre D, Procknow JJ. A new virus isolated from the human respiratory tract. Proc Soc Exp Biol Med. 1966 Jan;121(1):190-3.
(3) Warnes SL, Little ZR, Keevil CW. Human Coronavirus 229E Remains Infectious on Common Touch Surface Materials. mBio. 2015;6(6):e01697-15. Published 2015 Nov 10. doi:10.1128/mBio.01697-15
(4) Han J, Chen L, Duan SM, et al. Efficient and Quick Inactivation of SARS Coronavirus and Other Microbes Exposed to the Surfaces of Some Metal Catalysts Biomed Environ Sci. 2005;18(3):176–180.
(5) Duan SM, Zhao XS, Wen RF, Huang JJ, Pi GH, Zhang SX, Han J, Bi SL, Ruan L, Dong XP; Stability of SARS coronavirus in human specimens and environment and its sensitivity to heating and UV irradiation. SARS Research Team. Biomed Environ Sci. 2003 Sep;16(3):246-55.
(6) Chen YN, Hsueh YH, Hsieh CT, Tzou DY, Chang PL. Antiviral Activity of Graphene-Silver Nanocomposites against Non-Enveloped and Enveloped Viruses. Int J Environ Res Public Health. 2016;13(4):430. Published 2016 Apr 19. doi:10.3390/ijerph13040430
(7) Lv X, Wang P, Bai R, et al. Inhibitory effect of silver nanomaterials on transmissible virus-induced host cell infections. Biomaterials. 2014;35(13):4195–4203. doi:10.1016/j.biomaterials.2014.01.054
(8) Elguindi J, Wagner J, Rensing C. Genes involved in copper resistance influence survival of Pseudomonas aeruginosa on copper surfaces J Appl Microbiol. 2009 maggio;106(5):1448-55. doi: 10.1111/j.1365-2672.2009.04148.x.
(9) Michels HT, Noyce JO, Keevil CW. Effects of temperature and humidity on the efficacy of methicillin-resistant Staphylococcus aureus challenged antimicrobial materials containing silver and copper. Lett Appl Microbiol. 2009 Aug;49(2):191-5. doi: 10.1111/j.1472-765X.2009.02637.x.
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"Descrizione" about Coronavirus COVID-19. The symptoms. What to do? Review Consensus 9 by Al222 (17613 pt) | 2020-Mar-22 21:11 |
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The symptoms of Coronavirus COVID-19 are the same as those of the common flu:
If you have these symptoms here are the things not to do
and those to do:
or these numbers:
Basilicata: 800 99 66 88
Calabria: 800 76 76 76
Campania: 800 90 96 99
Emilia-Romagna: 800 033 033
Friuli Venezia Giulia: 800 500 300
Lazio: 800 11 88 00
Lombardia: 800 89 45 45
Marche: 800 93 66 77
Piemonte:
800 19 20 20 attivo 24 ore su 24
800 333 444 attivo dal lunedì al venerdì, dalle ore 8 alle 20
Provincia autonoma di Trento: 800 867 388
Provincia autonoma di Bolzano: 800 751 751
Puglia: 800 713 931
Sardegna: 800 311 377
Sicilia: 800 45 87 87
Toscana: 800 55 60 60
Umbria: 800 63 63 63
Val d’Aosta: 800 122 121
Veneto: 800 462 340
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"Descrizione" about COVID-19. Chitosan as prevention. Can it work? Review Consensus 10 by Al222 (17613 pt) | 2020-Mar-27 11:35 |
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COVID-19. Chitosan as prevention. Can it work?
Introduction
There is a question that should be answered today: while waiting for an approved vaccine, is it possible to contain the spread of the COVID-19 epidemic with a low toxicity drug that inhibits the virus/receptor ratio so as to prevent its entry?
Discussion
Coronaviruses usually cause only colds in healthy individuals and in the initial phase, while in the subsequent phase, the disease can lead to pneumonia with serious consequences in adults above the age of 60 and/or immunodepressed. Influenza epidemics explode every year between autumn and winter and, worldwide, infect about 3/5 million people with 250/500,000 deaths (1-2).
Let us now consider the typology in percentage of people affected by the virus: about 80% over 40 years old while the percentage is drastically reduced to 5.3% between 0 and 20 years old (3). The mortality rate was 2.8% for men and 1.7% for women while the highest mortality rate was 14.8% in the 80-year-old age group. Influences predominantly affect males, both in the older population and in the younger population (4) with a male-to-woman ratio of 1.3 in Europe and women develop a higher innate and adaptive immune response, which can be beneficial when encountering pathogens (5). These data confirm that the virus can enter more easily and cause more damage in those age groups where the immune system is less protected.
Now, since immunodepression is the facilitated way for the virus to create damage, a viable route could be to block the entry of the virus by first strengthening the immune system with natural antibacterial products and using a broad spectrum inhibitor to block the interactivity relationship between the virus and the human ACE2 receptor, a zincopeptidase membrane converted by angiotensin which is found distributed in the human body and more concentrated in kidney, testicles, heart. In particular, this blocking attempt must be made before the virus has entered our system as it may be contraindicated if the virus is already present (6).
It has been shown that the expression of ADA2 and several Ada2-mediated cell wall related genes (ALS2, PGA45, and ACE2) and efflux transporter genes (MDR1 and CDR1) have been significantly inhibited by chitosan (7) and the action of chitosan has been widely described by recent studies (8), so let us examine the likely benefits of this component.
Chitosan is a naturally abundant polysaccharide and has demonstrated excellent biocompatibility, biodegradability, mechanical strength and low toxicity.
It is obtained by alkaline N-deacetylation of chitin, which is the main component of the exoskeleton of crustaceans, such as shrimps, crabs and lobsters (9).
Many studies have focused on its function as a vector, in regenerative medicine, of bioactive molecules (10), of bone tissue regenerator (11), of its potential for tissue engineering on articular cartilage (12).
In vivo experiments showed that unmodified Chitosan nanoparticles were able to reverse fibrosis with a 100% survival rate at the end of the study, indicating the ability of Chitosan nanoparticles to provide functional collagenase to the fibrotic liver and making the use of collagen binding peptides unnecessary (13).
Because of its low toxicity and biodegradability properties, Chitosan has been used as an antimicrobial agent (14).
Chitosan and cationically modified chitosan (HTCC) are biomaterials that can be used to improve immune efficacy and improve immune response due to their promising mucoadhesive properties (15).
Conclusion
The combined action of a robust strengthening of immune defences combined with the intake of chitosan could be a preventive way of protection against COVID-19.
References__________________________________________________________________
(1) Gabriel G, Arck PC. Sex, immunity and influenza. J Infect Dis. 2014;209 Suppl 3:S93–S99. doi:10.1093/infdis/jiu020
(2) Iuliano AD, Roguski KM, Chang HH, Muscatello DJ, Palekar R, Tempia S, Cohen C, Gran JM, Schanzer D, Cowling BJ, Wu P, Kyncl J, Ang LW, Park M, Redlberger-Fritz M, Yu H, Espenhain L, Krishnan A, Emukule G, van Asten L, Pereira da Silva S, Aungkulanon S, Buchholz U, Widdowson MA, Bresee JS; Global Seasonal Influenza-associated Mortality Collaborator Network. Estimates of global seasonal influenza-associated respiratory mortality: a modelling study. Lancet. 2018 Mar 31;391(10127):1285-1300. doi: 10.1016/S0140-6736(17)33293-2
(3) Novel Coronavirus Pneumonia Emergency Response Epidemiology Team. Zhonghua Liu Xing Bing Xue Za Zhi. 2020;41(2):145–151. doi:10.3760/cma.j.issn.0254-6450.2020.02.003
(4) Jensen-Fangel S, Mohey R, Johnsen SP, Andersen PL, S'rensen HT, Ostergaard L. Gender Differences in Hospitalization Rates for Respiratory Tract Infections in Danish Youth Scand J infect Dis. 2004;36(1):31-6.
(5) Gabriel G, Arck PC. Sex, immunity and influenza. J Infect Dis. 2014;209 Suppl 3:S93–S99. doi:10.1093/infdis/jiu020
(6) Diaz JH. Hypothesis: angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may increase the risk of severe COVID-19 [published online ahead of print, 2020 Mar 18]. J Travel Med. 2020;taaa041. doi:10.1093/jtm/taaa041
(7) Shih PY, Liao YT, Tseng YK, Deng FS, Lin CH. A Potential Antifungal Effect of Chitosan Against Candida albicans Is Mediated via the Inhibition of SAGA Complex Component Expression and the Subsequent Alteration of Cell Surface Integrity. Front Microbiol. 2019;10:602. Published 2019 Mar 26. doi:10.3389/fmicb.2019.00602
(8) Foureaux G, Franca JR, Nogueira JC, et al. Ocular Inserts for Sustained Release of the Angiotensin-Converting Enzyme 2 Activator, Diminazene Aceturate, to Treat Glaucoma in Rats. PLoS One. 2015;10(7):e0133149. Published 2015 Jul 23. doi:10.1371/journal.pone.0133149
(9) Roberto Nisticò Aquatic-Derived Biomaterials for a Sustainable Future: A European Opportunity. Resources 2017, 6(4), 65; https://doi.org/10.3390/resources6040065
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"Descrizione" about Coronavirus COVID19. Part Four. Researching therapy Review Consensus 9 by Al222 (17613 pt) | 2020-May-13 18:08 |
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All the information contained in this article, in the video and in the site tiiips.com are purely informative, they should in no case be taken as a formulation of diagnosis or prescription of therapeutic treatments. Always ask your doctor.
What the latest studies say
No vaccine or drug has been approved to date
Monoclonal antibodies represent the main class of biotherapy for passive immunotherapy to combat viral infections (1). However, they have contraindications that need to be assessed on a case-by-case basis.
A temporary suggestion, probably resistant to new coronavirus mutations, is the use of angiotensin type 1 receptor blockers as a therapy to reduce aggressiveness and mortality from SARS-CoV-2 virus infections (2).
Approved nucleoside analogues marketed and approved in Japan under the name Avigan®, as well as ribavirin (Tribavirin or Virazole) and experimental nucleoside analogues such as remdesivir (a nucleotide-like formula currently under clinical trial for the treatment of Ebola virus infections) and galidesivir, may have potential on 2019-nCoV (3) but remdesivir appeared superior in efficacy to lopinavir/ritonavir and interferon beta versus MERS-CoV in a model of humanized transgenic mice (4). Regarding efficacy, favipiravir demonstrated an IC50 (concentration required to inhibit 50% of the target) of 601 μM versus 3.9 μM of ribavirin (5), but its use is approved with limitations as it has a risk of teratogenicity and embotoxicity (6).
This study provides the first generation of MERS-CoV fusion inhibitors with potencies in the low micromolar range (7).
Chloroquine phosphate, an already effective drug for the treatment of malaria, has been shown to have an apparent efficacy and acceptable safety against COVID-19 associated pneumonia in multicentre clinical trials conducted in China (8) tablet, 500mg twice per day for 10 days for patients diagnosed as mild, moderate and severe cases of novel coronavirus pneumonia and without contraindications to chloroquine (9) and already proposed 20 years ago by the authors of this study as effective in vitro against a wide range of viruses (10), another study also considers Hydroxychloroquine more potent and more tolerable (11).
Procalcitonin prohormone precursor of calcitonin, a diagnostic biomarker approved by the FDA in 2005, for patients with more severe symptoms of Coronavirus 2019 (COVID-19) (12) in intensive care unit (ICU).
In in vitro experiments were found to be effective against pangolin-borne coronavirus, cepharanthin alkaloid, selamectin, and mefloquine hydrochloride, a known malaria remedy (13).
People in old age are more likely to contract acute respiratory distress syndrome (ARDS) and this study suggests treatment with methylprednisolone (14), synthetic glucocorticoid and powerful anti-inflammatory.
Highly Standardized Mixture of Active Compounds Derived From Cultured Lentinula Edodes Mycelia (AHCC) action in promoting a protective response to a wide range of viral infections, and the current absence of effective vaccines, could support its use in the prevention of diseases provoked by human pathogenic coronavirus, including COVID-19 (15).
It is important to understand the defense dynamics of coronavirus to try to inhibit its replication, a very complex process aimed at preserving its large RNA genome. Replication and maturation of the virus have essential strengths in several proteases including Mpro or 3CL and papain-like protease (PLpro) both capable of generating mature proteins.
In previous MERS-CoV and SARS-CoV, disufiram (Tetraethylthiuram disulfide, Antabuse™) had been shown to inhibit papain protease and act as an allosteric inhibitor for MERS-CoV and as a competitive (or mixed) SARS-CoV inhibitor (16). It should not be co-administered with lopinavir/ritonavir (17).
In fact, PLpro plays a fundamental role in the defense of the virus as first of all it has the task of shaking off the proteins of the host cells that try, with the immune response, to neutralize the virus (18) and also plays a pharmacokinetic interaction on the stimulation of the host interferon through its deubiquitination activity (19).
Disulfiram is a well-known remedy against alcoholism, but has also recently demonstrated its effectiveness against cancer, leukemia and, importantly, a low toxicity (20). This study showed that the disulfiram/copper complex significantly induced the arrest of the cell cycle in the G2/M phase in MM.1S and RPMI8226 cells (21).
Between 2005 and 2009 some studies identified 6-mercaptopurine (anticancer drug approved by the US Food and Drug Administration (FDA) ), 6-thioguanine (a chemotherapeutic drug) and mycophenolic acid as compounds capable of inhibiting MERS-CoV PLpro by their synergistic effects and providing a basis for antiviral drugs (22) (23)
In 2018, during the PEDV pig epidemic, 6-thioguanine was suggested as a non-competitive PLpro inhibitor (24).
Another anti-malarial anti-infective drug, mefloquine, structurally related to quinine, which is often combined with artesunate (a semi-synthetic derivative of artemisininin) could provide results in the fight against coronavirus, but has contraindications for both long term treatment and potential side effects (25).
References_________________________________________________________
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(6) Nagata T, Lefor AK, Hasegawa M, Ishii M. Favipiravir: a new medication for the Ebola virus disease pandemic. Disaster Med Public Health Prep. 2015;9(1):79–81. doi:10.1017/dmp.2014.151
(7) Kandeel M, Yamamoto M, Al-Taher A, Watanabe A, Oh-Hashi K, Park BK, Kwon HJ, Inoue JI, Al-Nazawi M. Small Molecule Inhibitors of Middle East Respiratory Syndrome Coronavirus Fusion by Targeting Cavities on Heptad Repeat Trimers. Biomol Ther (Seoul). 2020 Mar 4. doi: 10.4062/biomolther.2019.202.
(8) Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends. 2020 Feb 19. doi: 10.5582/bst.2020.01047.
(9) Zhonghua Jie He He Hu Xi Za Zhi. multicenter collaboration group of Department of Science and Technology of Guangdong Province and Health Commission of Guangdong Province for chloroquine in the treatment of novel coronavirus pneumonia. Expert Consensus on Chloroquine Phosphate for the Treatment of Novel Coronavirus Pneumonia 2020;43(3):185–188. doi:10.3760/cma.j.issn.1001-0939.2020.03.009
(10) Colson P, Rolain JM, Raoult D. Chloroquine for the 2019 novel coronavirus SARS-CoV-2. Int J Antimicrob Agents. 2020 Feb 15:105923. doi: 10.1016/j.ijantimicag.2020.105923.
(11) Yao X, Ye F, Zhang M, Cui C, Huang B, Niu P, Liu X, Zhao L, Dong E, Song C, Zhan S, Lu R, Li H, Tan W, Liu D. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020 Mar 9. pii: ciaa237. doi: 10.1093/cid/ciaa237.
(12) Lippi G, Plebani M. Procalcitonin in patients with severe coronavirus disease 2019 (COVID-19): a meta-analysis. Clin Chim Acta. 2020 Mar 4. pii: S0009-8981(20)30106-6. doi: 10.1016/j.cca.2020.03.004.
Chanu Rhee, Using Procalcitonin to Guide Antibiotic Therapy, Open Forum Infectious Diseases, Volume 4, Issue 1, Winter 2017, ofw249, https://doi.org/10.1093/ofid/ofw249
(13) Fan HH, Wang LQ, Liu WL, An XP, Liu ZD, He XQ, Song LH, Tong YG. Repurposing of clinically approved drugs for treatment of coronavirus disease 2019 in a 2019-novel coronavirus (2019-nCoV) related coronavirus model. Chin Med J (Engl). 2020 Mar 6. doi: 10.1097/CM9.0000000000000797.
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