PMC:7068984 / 22485-27503 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7068984","sourcedb":"PMC","sourceid":"7068984","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7068984","text":"Antiviral treatments\nBased on the experience of fighting the epidemic SARS-CoV and MERS-CoV previously, we may learn some lessons for some treatment strategies against coronavirus [74]. Antiviral drugs and systemic corticosteroid treatment commonly used in clinical practice previously, including neuraminidase inhibitors (oseltamivir, peramivir, zanamivir, etc), ganciclovir, acyclovir, and ribavirin, as well as methylprednisolone [46, 75] for influenza virus, are invalid for COVID-19 and not recommended. Remdesivir (GS-5734) is a 1′-cyano-substituted adenosine nucleotide analog prodrug and shows broad-spectrum antiviral activity against several RNA viruses. Based on the data collected from in vitro cell line and mouse model, remdesivir could interfere with the NSP12 polymerase even in the setting of intact ExoN proofreading activity [76]. Remdesivir has been reported to treat the first US case of COVID-19 successfully [77]. Chloroquine is a repurposed drug with great potential to treat COVID-19. Chloroquine has been used to treat malaria for many years [78], with a mechanism that is not well understood against some viral infections. Several possible mechanisms are investigated: Chloroquine can inhibit pH-dependent steps of the replication of several viruses [79], with a potent effect on SARS-CoV infection and spread [80]. Moreover, chloroquine has immunomodulatory effects, suppressing the production/release of TNF-α and IL-6. It also works as a novel class of autophagy inhibitor [81], which may interfere with viral infection and replication. Several studies have found that chloroquine interfered with the glycosylation of cellular receptors of SARS-CoV [80] and functioned at both entry and at post-entry stages of the COVID-19 infection in Vero E6 cells [82]. A combination of remdesivir and chloroquine was proven to effectively inhibit the recently emerged SARS-CoV-2 in vitro.\nScientists previously confirmed that the protease inhibitors lopinavir and ritonavir, used to treat infection with human immunodeficiency virus (HIV) [83], could improve the outcome of MERS-CoV [84] and SARS-CoV [85] patients. It has reported that β-coronavirus viral loads of a COVID-19 patient in Korea significantly decreased after lopinavir/ritonavir (Kaletra®, AbbVie, North Chicago, IL, USA) treatment [86]. Additionally, clinicians combined Chinese and Western medicine treatment including lopinavir/ritonavir (Kaletra®), arbidol, and Shufeng Jiedu Capsule (SFJDC, a traditional Chinese medicine) and gained significant improvement in pneumonia associated symptoms in Shanghai Public Health Clinical Center, China [87].The other antiviral drugs include nitazoxanide, favipiravir, nafamostat, and so on (See Table 1 for details).\nTable 1 Common and potent antiviral drugs\nStatus Drugs Action mode Anti-infective mechanism Target diseases Ref.\nApproved Lopinavir/Ritonavir Protease inhibitors Inhibiting HIV-1 protease for protein cleavage, resulting in non-infectious, immature viral particles HIV/AIDS, SARS, MERS [83–85]\nApproved, Investigational, Vet approved Chloroquine 9-aminoquinolin Increasing endosomal pH, immunomodulating, autophagy inhibitors Malaria, autoimmune disease [79–82]\nExperimental Remdesivir (GS-5734) Nucleotide analogue prodrug Interfering with virus post-entry Ebola, SARS, MERS\n(A wide array of RNA viruses) [76, 88, 89]\nInvestigational Nafamostat Synthetic serine protease inhibitor Prevents membrane fusion by reducing the release of cathepsin B; anticoagulant activities Influenza, MERS, Ebola [90, 91]\nApproved Ribavirin Synthetic guanosine nucleoside Interfering with the synthesis of viral mRNA (a broad-spectrum activity against several RNA and DNA viruses) HCV, SARS, MERS [92–94]\nApproved Oseltamivir Neuraminidase inhibitor Inhibiting the activity of the viral neuraminidase enzyme, preventing budding from the host cell, viral replication, and infectivity Influenza viruses A [95, 96]\nApproved Penciclovir/ Acyclovir Nucleoside analog A synthetic acyclic guanine derivative, resulting in chain termination HSV, VZV [97]\nApproved, Investigational Ganciclovir Nucleoside analog Potent inhibitor of the Herpesvirus family including cytomegalovirus AIDS-associated cytomegalovirus infections [98]\nInvestigational Favipiravir (T-705) Nucleoside analog: Viral RNA polymerase inhibitor Acting on viral genetic copying to prevent its reproduction, without affecting host cellular RNA or DNA synthesis Ebola, influenza A(H1N1) [99–101]\nApproved, Investigational, Vet approved Nitazoxanide Antiprotozoal agent Modulating the survival, growth, and proliferation of a range of extracellular and intracellular protozoa, helminths, anaerobic and microaerophilic bacteria, viruses A wide range of viruses including human/animal coronaviruses [102–104]\nHIV Human immunodeficiency virus, AIDS Acquired immune deficiency syndrome, SARS Severe acute respiratory syndrome, MERS Middle East respiratory syndrome, HCV Hepatitis C virus, HSV Herpes simplex virus, VZV Varicella-zoster 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