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Insights into antiviral mechanisms of remdesivir, lopinavir/ritonavir and chloroquine/hydroxychloroquine affecting the new SARS-CoV-2.
Biomed Pharmacother. 2020 Nov; 131:110668.BP

Abstract

Coronavirus disease 2019 (COVID-19) is a kind of viral pneumonia with an unusual outbreak in Wuhan, China, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There is currently no licensed antiviral treatment available to prevent human CoV infection. The widespread clinical use and existing knowledge on antiviral mechanisms of remdesivir, lopinavir/ritonavir and chloroquine/hydroxychloroquine in the treatment of previous epidemic diseases, namely, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), may be helpful in the combat with novel SARS-CoV-2 infection. Recent clinical evidence didn't confirm the beneficial role of lopinavir/ritonavir and chloroquine/hydroxychloroquine for COVID-19 patients and their use was reassessed. We provide an overview of the current evidence into the mechanisms of action of these available drugs which are repurposed for treatment of the new virus. Available data identifies remdesivir as an adenosine analogue that can target the RNA-dependent RNA polymerase and block viral RNA synthesis. It has been a promising antiviral drug against a wide array of RNA viruses. 3CLpro is a major CoV protease that cleaves the large replicase polyproteins during viral replication and can be targeted by the protease inhibitor lopinavir/ritonavir but the clinical effects are controversial. Chloroquine/Hydroxychloroquine could impair the replication of SARSCoV-2 by multiple mechanisms and their immunomodulatory properties could ameliorate clinical manifestations that are mediated by immune reactions of the host although its beneficial effects are under question and need to be proven at the clinical level. Existing in vitro and in vivo evidence delineate the molecular mechanisms of these drugs in CoV-infected cells. Numerous studies demonstrated the ability of remdesivir to inhibit SARS-CoV-2 replication but future research would be needed to understand the exact mode of action of lopinavir/ritonavir and chloroquine/hydroxychloroquine in SARS-CoV-2 infected cells and to use this knowledge in the treatment of the current COVID-19.

Authors+Show Affiliations

Tchaikapharma High Quality Medicines Inc., Science Department, 1 G.M. Dimitrov Blvd, 1172, Sofia, Bulgaria. Electronic address: k.uzunova.hq@tchaikapharma.com.Tchaikapharma High Quality Medicines Inc., Science Department, 1 G.M. Dimitrov Blvd, 1172, Sofia, Bulgaria. Electronic address: e.filipova.hq@tchaikapharma.com.Tchaikapharma High Quality Medicines Inc., Science Department, 1 G.M. Dimitrov Blvd, 1172, Sofia, Bulgaria. Electronic address: v.pavlova.hq@tchaikapharma.com.Medical University, Dean of Faculty of Pharmacy, 1 Sv. Kliment Ohriski Str., 5800, Pleven, Bulgaria. Electronic address: t.vekov.mu.pleven@abv.bg.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

32861965

Citation

Uzunova, Katya, et al. "Insights Into Antiviral Mechanisms of Remdesivir, Lopinavir/ritonavir and Chloroquine/hydroxychloroquine Affecting the New SARS-CoV-2." Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, vol. 131, 2020, p. 110668.
Uzunova K, Filipova E, Pavlova V, et al. Insights into antiviral mechanisms of remdesivir, lopinavir/ritonavir and chloroquine/hydroxychloroquine affecting the new SARS-CoV-2. Biomed Pharmacother. 2020;131:110668.
Uzunova, K., Filipova, E., Pavlova, V., & Vekov, T. (2020). Insights into antiviral mechanisms of remdesivir, lopinavir/ritonavir and chloroquine/hydroxychloroquine affecting the new SARS-CoV-2. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 131, 110668. https://doi.org/10.1016/j.biopha.2020.110668
Uzunova K, et al. Insights Into Antiviral Mechanisms of Remdesivir, Lopinavir/ritonavir and Chloroquine/hydroxychloroquine Affecting the New SARS-CoV-2. Biomed Pharmacother. 2020;131:110668. PubMed PMID: 32861965.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Insights into antiviral mechanisms of remdesivir, lopinavir/ritonavir and chloroquine/hydroxychloroquine affecting the new SARS-CoV-2. AU - Uzunova,Katya, AU - Filipova,Elena, AU - Pavlova,Velichka, AU - Vekov,Toni, Y1 - 2020/08/24/ PY - 2020/05/19/received PY - 2020/08/12/revised PY - 2020/08/20/accepted PY - 2020/8/31/pubmed PY - 2020/11/11/medline PY - 2020/8/31/entrez KW - Antiviral mechanism KW - Chloroquine/hydroxychloroquine KW - Lopinavir/ritonavir KW - Remdesivir KW - SARS-CoV-2 SP - 110668 EP - 110668 JF - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JO - Biomed Pharmacother VL - 131 N2 - Coronavirus disease 2019 (COVID-19) is a kind of viral pneumonia with an unusual outbreak in Wuhan, China, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There is currently no licensed antiviral treatment available to prevent human CoV infection. The widespread clinical use and existing knowledge on antiviral mechanisms of remdesivir, lopinavir/ritonavir and chloroquine/hydroxychloroquine in the treatment of previous epidemic diseases, namely, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), may be helpful in the combat with novel SARS-CoV-2 infection. Recent clinical evidence didn't confirm the beneficial role of lopinavir/ritonavir and chloroquine/hydroxychloroquine for COVID-19 patients and their use was reassessed. We provide an overview of the current evidence into the mechanisms of action of these available drugs which are repurposed for treatment of the new virus. Available data identifies remdesivir as an adenosine analogue that can target the RNA-dependent RNA polymerase and block viral RNA synthesis. It has been a promising antiviral drug against a wide array of RNA viruses. 3CLpro is a major CoV protease that cleaves the large replicase polyproteins during viral replication and can be targeted by the protease inhibitor lopinavir/ritonavir but the clinical effects are controversial. Chloroquine/Hydroxychloroquine could impair the replication of SARSCoV-2 by multiple mechanisms and their immunomodulatory properties could ameliorate clinical manifestations that are mediated by immune reactions of the host although its beneficial effects are under question and need to be proven at the clinical level. Existing in vitro and in vivo evidence delineate the molecular mechanisms of these drugs in CoV-infected cells. Numerous studies demonstrated the ability of remdesivir to inhibit SARS-CoV-2 replication but future research would be needed to understand the exact mode of action of lopinavir/ritonavir and chloroquine/hydroxychloroquine in SARS-CoV-2 infected cells and to use this knowledge in the treatment of the current COVID-19. SN - 1950-6007 UR - https://www.unboundmedicine.com/medline/citation/32861965/Insights_into_antiviral_mechanisms_of_remdesivir_lopinavir/ritonavir_and_chloroquine/hydroxychloroquine_affecting_the_new_SARS_CoV_2_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0753-3322(20)30861-1 DB - PRIME DP - Unbound Medicine ER -