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Antiviral therapy for COVID-19: Derivation of optimal strategy based on past antiviral and favipiravir experiences

Favipiravir, a broad-spectrum RNA-dependent RNA polymerase inhibitor, inhibits the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at significantly lower concentrations than the plasma trough levels achieved by the dosage adopted for influenza treatment and exhibits effic...

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Autores principales: Shiraki, Kimiyasu, Sato, Noriaki, Sakai, Kaoru, Matsumoto, Shirou, Kaszynski, Richard H., Takemoto, Masaya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8806403/
https://www.ncbi.nlm.nih.gov/pubmed/35121001
http://dx.doi.org/10.1016/j.pharmthera.2022.108121
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author Shiraki, Kimiyasu
Sato, Noriaki
Sakai, Kaoru
Matsumoto, Shirou
Kaszynski, Richard H.
Takemoto, Masaya
author_facet Shiraki, Kimiyasu
Sato, Noriaki
Sakai, Kaoru
Matsumoto, Shirou
Kaszynski, Richard H.
Takemoto, Masaya
author_sort Shiraki, Kimiyasu
collection PubMed
description Favipiravir, a broad-spectrum RNA-dependent RNA polymerase inhibitor, inhibits the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at significantly lower concentrations than the plasma trough levels achieved by the dosage adopted for influenza treatment and exhibits efficacy against coronavirus disease 2019 (COVID-19) pneumonia. Although high doses of favipiravir are required due to the molecule being a purine analog, its conversion into the active form in infected cells with active viral RNA synthesis enhances the antiviral specificity and selectivity as a chain terminator with lethal mutagenesis. Another characteristic feature is the lack of generation of favipiravir-resistant virus. COVID-19 pneumonia is caused by strong cell-mediated immunity against virus-infected cells, and the inflammatory response induced by adaptive immunity continues to peak for 3 to 5 days despite antiviral treatment. This has also been observed in herpes zoster (HZ) and cytomegalovirus (CMV) pneumonia. Inflammation due to an immune response may mask the effectiveness of favipiravir against COVID-19 pneumonia. Favipiravir significantly shortened the recovery time in patients with mild COVID-19 pneumonia by 3 days with the start of treatment by the 5th day of symptom onset. Since both CMV and COVID-19 pneumonia are caused by adaptive immunity and prevention of cytomegalovirus pneumonia is the standard treatment due to difficulties in treating refractory CMV pneumonia, COVID-19 pneumonia should be prevented with early treatment as well. In the present study, we have comprehensively reviewed the optimal antiviral therapy for COVID-19 based on clinical trials of favipiravir for the treatment of COVID-19 pneumonia and the concurrently established therapies for other viral infections, particularly HZ and CMV pneumonia. Optimally, antivirals should be administered immediately after COVID-19 diagnosis, similar to that after influenza diagnosis, to prevent COVID-19 pneumonia and complications resulting from microangiopathy.
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spelling pubmed-88064032022-02-02 Antiviral therapy for COVID-19: Derivation of optimal strategy based on past antiviral and favipiravir experiences Shiraki, Kimiyasu Sato, Noriaki Sakai, Kaoru Matsumoto, Shirou Kaszynski, Richard H. Takemoto, Masaya Pharmacol Ther Article Favipiravir, a broad-spectrum RNA-dependent RNA polymerase inhibitor, inhibits the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at significantly lower concentrations than the plasma trough levels achieved by the dosage adopted for influenza treatment and exhibits efficacy against coronavirus disease 2019 (COVID-19) pneumonia. Although high doses of favipiravir are required due to the molecule being a purine analog, its conversion into the active form in infected cells with active viral RNA synthesis enhances the antiviral specificity and selectivity as a chain terminator with lethal mutagenesis. Another characteristic feature is the lack of generation of favipiravir-resistant virus. COVID-19 pneumonia is caused by strong cell-mediated immunity against virus-infected cells, and the inflammatory response induced by adaptive immunity continues to peak for 3 to 5 days despite antiviral treatment. This has also been observed in herpes zoster (HZ) and cytomegalovirus (CMV) pneumonia. Inflammation due to an immune response may mask the effectiveness of favipiravir against COVID-19 pneumonia. Favipiravir significantly shortened the recovery time in patients with mild COVID-19 pneumonia by 3 days with the start of treatment by the 5th day of symptom onset. Since both CMV and COVID-19 pneumonia are caused by adaptive immunity and prevention of cytomegalovirus pneumonia is the standard treatment due to difficulties in treating refractory CMV pneumonia, COVID-19 pneumonia should be prevented with early treatment as well. In the present study, we have comprehensively reviewed the optimal antiviral therapy for COVID-19 based on clinical trials of favipiravir for the treatment of COVID-19 pneumonia and the concurrently established therapies for other viral infections, particularly HZ and CMV pneumonia. Optimally, antivirals should be administered immediately after COVID-19 diagnosis, similar to that after influenza diagnosis, to prevent COVID-19 pneumonia and complications resulting from microangiopathy. Elsevier Inc. 2022-07 2022-02-01 /pmc/articles/PMC8806403/ /pubmed/35121001 http://dx.doi.org/10.1016/j.pharmthera.2022.108121 Text en © 2022 Elsevier Inc. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Shiraki, Kimiyasu
Sato, Noriaki
Sakai, Kaoru
Matsumoto, Shirou
Kaszynski, Richard H.
Takemoto, Masaya
Antiviral therapy for COVID-19: Derivation of optimal strategy based on past antiviral and favipiravir experiences
title Antiviral therapy for COVID-19: Derivation of optimal strategy based on past antiviral and favipiravir experiences
title_full Antiviral therapy for COVID-19: Derivation of optimal strategy based on past antiviral and favipiravir experiences
title_fullStr Antiviral therapy for COVID-19: Derivation of optimal strategy based on past antiviral and favipiravir experiences
title_full_unstemmed Antiviral therapy for COVID-19: Derivation of optimal strategy based on past antiviral and favipiravir experiences
title_short Antiviral therapy for COVID-19: Derivation of optimal strategy based on past antiviral and favipiravir experiences
title_sort antiviral therapy for covid-19: derivation of optimal strategy based on past antiviral and favipiravir experiences
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8806403/
https://www.ncbi.nlm.nih.gov/pubmed/35121001
http://dx.doi.org/10.1016/j.pharmthera.2022.108121
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