Antiretroviral drug activity and potential for pre-exposure prophylaxis against COVID-19 and HIV infection
COVID-19 is the disease caused by SARS-CoV-2 which has led to 2,643,000 deaths worldwide, a number which is rapidly increasing. Urgent studies to identify new antiviral drugs, repurpose existing drugs, or identify drugs that can target the overactive immune response are ongoing. Antiretroviral drugs (ARVs) have been tested in past human coronavirus infections, and also against SARS-CoV-2, but a trial of lopinavir and ritonavir failed to show any clinical benefit in COVID-19. However, there is limited data as to the course of COVID-19 in people living with HIV, with some studies showing a decreased mortality for those taking certain ARV regimens. We hypothesized that ARVs other than lopinavir and ritonavir might be responsible for some protection against the progression of COVID-19. Here, we used chemoinformatic analyses to predict which ARVs would bind and potentially inhibit the SARS-CoV-2 main protease (Mpro) or RNA-dependent-RNA-polymerase (RdRp) enzymes in silico. The drugs predicted to bind the SARS-CoV-2 Mpro included the protease inhibitors atazanavir and indinavir. The ARVs predicted to bind the catalytic site of the RdRp included Nucleoside Reverse Transcriptase Inhibitors, abacavir, emtricitabine, zidovudine, and tenofovir. 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 in clinical trials. Further studies are needed to establish the activity of ARVs for treatment or prevention of SARS-CoV-2 infection .Communicated by Ramaswamy H. Sarma.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:40 |
|---|---|
| Enthalten in: |
Journal of biomolecular structure & dynamics - 40(2022), 16 vom: 17. Okt., Seite 7367-7380 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Copertino, Dennis C [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 13.09.2022 Date Revised 02.10.2023 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1080/07391102.2021.1901144 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM322905958 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM322905958 | ||
| 003 | DE-627 | ||
| 005 | 20231225183031.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1080/07391102.2021.1901144 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1076.xml |
| 035 | |a (DE-627)NLM322905958 | ||
| 035 | |a (NLM)33734021 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Copertino, Dennis C |c Jr |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Antiretroviral drug activity and potential for pre-exposure prophylaxis against COVID-19 and HIV infection |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 13.09.2022 | ||
| 500 | |a Date Revised 02.10.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a COVID-19 is the disease caused by SARS-CoV-2 which has led to 2,643,000 deaths worldwide, a number which is rapidly increasing. Urgent studies to identify new antiviral drugs, repurpose existing drugs, or identify drugs that can target the overactive immune response are ongoing. Antiretroviral drugs (ARVs) have been tested in past human coronavirus infections, and also against SARS-CoV-2, but a trial of lopinavir and ritonavir failed to show any clinical benefit in COVID-19. However, there is limited data as to the course of COVID-19 in people living with HIV, with some studies showing a decreased mortality for those taking certain ARV regimens. We hypothesized that ARVs other than lopinavir and ritonavir might be responsible for some protection against the progression of COVID-19. Here, we used chemoinformatic analyses to predict which ARVs would bind and potentially inhibit the SARS-CoV-2 main protease (Mpro) or RNA-dependent-RNA-polymerase (RdRp) enzymes in silico. The drugs predicted to bind the SARS-CoV-2 Mpro included the protease inhibitors atazanavir and indinavir. The ARVs predicted to bind the catalytic site of the RdRp included Nucleoside Reverse Transcriptase Inhibitors, abacavir, emtricitabine, zidovudine, and tenofovir. 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 in clinical trials. Further studies are needed to establish the activity of ARVs for treatment or prevention of SARS-CoV-2 infection .Communicated by Ramaswamy H. Sarma | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a HIV | |
| 650 | 4 | |a PrEP | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a antiretrovirals | |
| 650 | 4 | |a docking | |
| 650 | 7 | |a Lopinavir |2 NLM | |
| 650 | 7 | |a 2494G1JF75 |2 NLM | |
| 650 | 7 | |a RNA |2 NLM | |
| 650 | 7 | |a 63231-63-0 |2 NLM | |
| 650 | 7 | |a RNA-Dependent RNA Polymerase |2 NLM | |
| 650 | 7 | |a EC 2.7.7.48 |2 NLM | |
| 650 | 7 | |a Ritonavir |2 NLM | |
| 650 | 7 | |a O3J8G9O825 |2 NLM | |
| 700 | 1 | |a Casado Lima, Bruno C |e verfasserin |4 aut | |
| 700 | 1 | |a Duarte, Rodrigo R R |e verfasserin |4 aut | |
| 700 | 1 | |a Powell, Timothy R |e verfasserin |4 aut | |
| 700 | 1 | |a Ormsby, Christopher E |e verfasserin |4 aut | |
| 700 | 1 | |a Wilkin, Timothy |e verfasserin |4 aut | |
| 700 | 1 | |a Gulick, Roy M |e verfasserin |4 aut | |
| 700 | 1 | |a de Mulder Rougvie, Miguel |e verfasserin |4 aut | |
| 700 | 1 | |a Nixon, Douglas F |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of biomolecular structure & dynamics |d 1985 |g 40(2022), 16 vom: 17. Okt., Seite 7367-7380 |w (DE-627)NLM012639974 |x 1538-0254 |7 nnns |
| 773 | 1 | 8 | |g volume:40 |g year:2022 |g number:16 |g day:17 |g month:10 |g pages:7367-7380 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1080/07391102.2021.1901144 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 40 |j 2022 |e 16 |b 17 |c 10 |h 7367-7380 | ||