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.

There have been more than 116,000 recorded deaths worldwide to-date caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), the etiological agent of the Coronavirus Disease 2019 (COVID-19), and over 1.8 million individuals are currently infected. Although there are now hundreds of clinical trials for COVID-19, there are currently no effective licensed treatments, while the numbers of infected individuals continue to rise at an exponential rate in many parts of the world. Here, we used a data-driven approach utilizing connectivity mapping and the transcriptional signature of lung carcinoma cells infected with SARS-CoV-2, to search for drugs across the spectrum of medicine that have repurposing potential for treating COVID-19. We also performed chemoinformatic analyses to test whether the identified compounds were predicted to physically interact with the SARS-CoV-2 RNA-dependent RNA polymerase or main protease enzymes. Our study identified commonly prescribed FDA-approved molecules as important candidates for drug repositioning against COVID-19, including flupentixol, reserpine, fluoxetine, trifluoperazine, sunitinib, atorvastatin, raloxifene, butoconazole, and metformin. These drugs should not be taken for treating or preventing COVID-19 without a doctor’s advice, as further research and clinical trials are now needed to elucidate their efficacy for this purpose.

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.

There have been more than 116,000 recorded deaths worldwide to-date caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), the etiological agent of the Coronavirus Disease 2019 (COVID-19), and over 1.8 million individuals are currently infected. Although there are now hundreds of clinical trials for COVID-19, there are currently no effective licensed treatments, while the numbers of infected individuals continue to rise at an exponential rate in many parts of the world. Here, we used a data-driven approach utilizing connectivity mapping and the transcriptional signature of lung carcinoma cells infected with SARS-CoV-2, to search for drugs across the spectrum of medicine that have repurposing potential for treating COVID-19. We also performed chemoinformatic analyses to test whether the identified compounds were predicted to physically interact with the SARS-CoV-2 RNA-dependent RNA polymerase or main protease enzymes. Our study identified commonly prescribed FDA-approved molecules as important candidates for drug repositioning against COVID-19, including flupentixol, reserpine, fluoxetine, trifluoperazine, sunitinib, atorvastatin, raloxifene, butoconazole, and metformin. These drugs should not be taken for treating or preventing COVID-19 without a doctor’s advice, as further research and clinical trials are now needed to elucidate their efficacy for this purpose.