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Compounds with Therapeutic Potential against Novel Respiratory 2019 Coronavirus.
Antimicrob Agents Chemother. 2020 04 21; 64(5)AA

Abstract

Currently, the expansion of the novel human respiratory coronavirus (known as SARS-CoV-2 [severe acute respiratory syndrome coronavirus 2], COVID-2019 [coronavirus disease 2019], or 2019-nCoV [2019 novel coronavirus]) has stressed the need for therapeutic alternatives to alleviate and stop this new epidemic. The previous epidemics of infections by high-morbidity human coronaviruses, such as SARS-CoV in 2003 and the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, prompted the characterization of compounds that could be potentially active against the currently emerging novel coronavirus, SARS-CoV-2. The most promising compound is remdesivir (GS-5734), a nucleotide analog prodrug currently in clinical trials for treating Ebola virus infections. Remdesivir inhibited the replication of SARS-CoV and MERS-CoV in tissue cultures, and it displayed efficacy in nonhuman animal models. In addition, a combination of the human immunodeficiency virus type 1 (HIV-1) protease inhibitors lopinavir/ritonavir and interferon beta (LPV/RTV-IFN-β) was shown to be effective in patients infected with SARS-CoV. LPV/RTV-IFN-β also improved clinical parameters in marmosets and mice infected with MERS-CoV. Remarkably, the therapeutic efficacy of remdesivir appeared to be superior to that of LPV/RTV-IFN-β against MERS-CoV in a transgenic humanized mouse model. The relatively high mortality rates associated with these three novel human coronavirus infections, SARS-CoV, MERS-CoV, and SARS-CoV-2, have suggested that proinflammatory responses might play a role in the pathogenesis. It remains unknown whether the generated inflammatory state should be targeted. Therapeutics that target the coronavirus alone might not be able to reverse highly pathogenic infections. This minireview aims to provide a summary of therapeutic compounds that have shown potential in fighting SARS-CoV-2 infections.

Authors+Show Affiliations

IrsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona (UAB), Badalona, Spain mmartinez@irsicaixa.es.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

32152082

Citation

Martinez, Miguel Angel. "Compounds With Therapeutic Potential Against Novel Respiratory 2019 Coronavirus." Antimicrobial Agents and Chemotherapy, vol. 64, no. 5, 2020.
Martinez MA. Compounds with Therapeutic Potential against Novel Respiratory 2019 Coronavirus. Antimicrob Agents Chemother. 2020;64(5).
Martinez, M. A. (2020). Compounds with Therapeutic Potential against Novel Respiratory 2019 Coronavirus. Antimicrobial Agents and Chemotherapy, 64(5). https://doi.org/10.1128/AAC.00399-20
Martinez MA. Compounds With Therapeutic Potential Against Novel Respiratory 2019 Coronavirus. Antimicrob Agents Chemother. 2020 04 21;64(5) PubMed PMID: 32152082.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Compounds with Therapeutic Potential against Novel Respiratory 2019 Coronavirus. A1 - Martinez,Miguel Angel, Y1 - 2020/04/21/ PY - 2020/3/11/pubmed PY - 2020/4/25/medline PY - 2020/3/11/entrez KW - SARS-CoV-2 KW - antiviral agents KW - coronavirus JF - Antimicrobial agents and chemotherapy JO - Antimicrob Agents Chemother VL - 64 IS - 5 N2 - Currently, the expansion of the novel human respiratory coronavirus (known as SARS-CoV-2 [severe acute respiratory syndrome coronavirus 2], COVID-2019 [coronavirus disease 2019], or 2019-nCoV [2019 novel coronavirus]) has stressed the need for therapeutic alternatives to alleviate and stop this new epidemic. The previous epidemics of infections by high-morbidity human coronaviruses, such as SARS-CoV in 2003 and the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, prompted the characterization of compounds that could be potentially active against the currently emerging novel coronavirus, SARS-CoV-2. The most promising compound is remdesivir (GS-5734), a nucleotide analog prodrug currently in clinical trials for treating Ebola virus infections. Remdesivir inhibited the replication of SARS-CoV and MERS-CoV in tissue cultures, and it displayed efficacy in nonhuman animal models. In addition, a combination of the human immunodeficiency virus type 1 (HIV-1) protease inhibitors lopinavir/ritonavir and interferon beta (LPV/RTV-IFN-β) was shown to be effective in patients infected with SARS-CoV. LPV/RTV-IFN-β also improved clinical parameters in marmosets and mice infected with MERS-CoV. Remarkably, the therapeutic efficacy of remdesivir appeared to be superior to that of LPV/RTV-IFN-β against MERS-CoV in a transgenic humanized mouse model. The relatively high mortality rates associated with these three novel human coronavirus infections, SARS-CoV, MERS-CoV, and SARS-CoV-2, have suggested that proinflammatory responses might play a role in the pathogenesis. It remains unknown whether the generated inflammatory state should be targeted. Therapeutics that target the coronavirus alone might not be able to reverse highly pathogenic infections. This minireview aims to provide a summary of therapeutic compounds that have shown potential in fighting SARS-CoV-2 infections. SN - 1098-6596 UR - https://www.unboundmedicine.com/medline/citation/32152082/Compounds_with_Therapeutic_Potential_against_Novel_Respiratory_2019_Coronavirus_ L2 - http://aac.asm.org/cgi/pmidlookup?view=long&pmid=32152082 DB - PRIME DP - Unbound Medicine ER -