Antiretroviral Drug Activity and Potential for Pre-Exposure Prophylaxis Against COVID-19 and HIV Infection

Dennis C. Copertino Jr., Bruno Lima, Rodrigo Duarte, Timothy Wilkin, Roy Gulick, Miguel de Mulder Rougvie, Douglas Nixon

10.26434/chemrxiv.12250199.v1

Research curated

Abstract

COVID-19 is the disease caused by SARS-CoV-2, and has led to over 250,000 deaths by May 2020. Urgent studies to identify new antiviral drugs, repurpose existing drugs, or identify those drugs that can specifically target the overactive immune response are ongoing around the world. Antiretroviral drugs (ARVs) have been tested in past human coronavirus infections, and also against SARS-CoV-2, but a recent clinical trial of lopinavir and ritonavir failed to show any clinical benefit in COVID-19 disease. However, anecdotal reports suggest either reduced infection or a course of milder COVID-19 disease in people living with HIV (PLWH) on ARVs. We hypothesized ARVs other than lopinavir and ritonavir might be responsible for such effects. Here, we used chemoinformatic analyses to predict which ARVs would bind and potentially inhibit the SARS-CoV-2 main protease or RNA-dependent RNA polymerase enzymes, and identified a number of ARVs which bind to SARS-CoV-2 enzymes in silico. Our study identified HIV nucleoside/nucleotide analogue reverse transcriptase inhibitors (abacavir, emtricitabine, lamivudine, tenofovir, zidovudine), HIV protease inhibitors (ASC09, atazanavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir) and an HIV pharmacokinetic booster (cobicistat), as drug candidates with effective in silico binding to one or both viral enzymes. Tenofovir and emtricitabine are FDA-approved as HIV pre-exposure prophylaxis (PrEP) and have an extensive safety profile of use in populations without HIV. Existing or new combinations of antiretroviral drugs could potentially prevent or ameliorate the course of COVID-19, if shown to inhibit SARS-CoV-2 in vitro and/or in clinical trials. Further studies are needed to establish the activity of ARVs for treatment or prevention of SARS-CoV-2 infection.

Source: ChemRxiv

Related molecules

Name	Synonyms	Genes
Zidovudine	azidothymidine
Tenofovir	Anhydrous tenofovir, Tenofovir anhydrous
RNA dependent RNA polymerase	RDR, viral RNA polymerase, RdRp, nsp12	rep, ORF1a-1b, RdRp
TMC-310911	ASC09, ASC-09
Emtricitabine	(−)-(2R,5S)-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine, (−)-FTC
Tipranavir
Abacavir
Saquinavir
Nelfinavir
Cobicistat
3C-like protease	3CLpro, Mpro, SARS coronavirus main peptidase, 3CLpro-SARS-CoV-2	rep, ORF1a-1b
Lamivudine
Atazanavir
Ritonavir
Lopinavir
Indinavir

Related interactions

Target	Drug	Type	Result
RNA dependent RNA polymerase	Abacavir	Computational	positive
RNA dependent RNA polymerase	Emtricitabine	Computational	positive
RNA dependent RNA polymerase	Atazanavir	Computational	positive
RNA dependent RNA polymerase	Saquinavir	Computational	positive
RNA dependent RNA polymerase	Zidovudine	In vitro	positive
RNA dependent RNA polymerase	Lopinavir	Computational	positive
RNA dependent RNA polymerase	TMC-310911	Computational	positive
RNA dependent RNA polymerase	Tenofovir	Computational	positive
3C-like protease	Tipranavir	Computational	positive
3C-like protease	Nelfinavir	Computational	positive
3C-like protease	TMC-310911	Computational	positive
RNA dependent RNA polymerase	Cobicistat	Computational	positive
3C-like protease	Indinavir	Computational	positive
3C-like protease	Saquinavir	Computational	positive
3C-like protease	Cobicistat	Computational	positive
RNA dependent RNA polymerase	Lamivudine	Computational	positive
RNA dependent RNA polymerase	Ritonavir	Computational	positive
3C-like protease	Lopinavir	Computational	positive
3C-like protease	Atazanavir	Computational	positive
3C-like protease	Ritonavir	Computational	positive