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

07 May 2020, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

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.

Keywords

Abacavir
Emtricitabine
Lamivudine
Tenofovir
Zidovudine
Atazanavir
Indinavir
lopinavir
nelfinavir
ritonavir
saquinavir
tipranavir
cobicistat
HIV
COVID-19
SARS-CoV-2
SARS-CoV
MERS
PrEP
ARV
Antiretroviral drugs
Pre-exposure Prophylaxis
in silico
docking
PLANTS
NRTI
NNRTI
PI
Protease inhibitor
RdRp
Mpro

Supplementary materials

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Supplemental Table 1
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Supplemental Table 2
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