Early combination treatment with existing HIV antivirals: an effective treatment for COVID-19?

Area of Science:

• Virology
• Drug Discovery
• Computational Chemistry

Background:

• Coronavirus disease 19 (COVID-19) poses a significant global health challenge.
• No universally effective therapy currently exists for COVID-19.
• Existing antiviral medications for Human Immunodeficiency Virus (HIV) are being investigated for repurposing.

Purpose of the Study:

• To evaluate the efficacy of existing HIV antivirals as a combination therapy for COVID-19.
• To computationally assess the binding interactions of HIV drugs with key SARS-CoV-2 viral proteins.

Main Methods:

• Utilized crystal structures of SARS-CoV-2 main protease (Mpro) and RNA-dependent RNA polymerase (RdRp).
• Employed molecular docking simulations using AutoDock 4.2.6 with the Lamarckian genetic algorithm.
• Assessed binding affinities and interactions of HIV protease inhibitors and nucleoside analogues with viral targets.

Main Results:

• Lopinavir, ritonavir, and darunavir demonstrated strong interactions with the SARS-CoV-2 Mpro binding sites.
• Remdesivir, tenofovir, emtricitabine, and lamivudine showed potential for incorporation into the SARS-CoV-2 RdRp.
• These nucleoside analogues exhibited comparable inhibition constants (Ki) to natural substrates.

Conclusions:

• HIV protease inhibitors and nucleoside analogues show promise for COVID-19 treatment.
• A combination therapy involving a protease inhibitor and two nucleoside analogues warrants clinical investigation.
• Repurposing HIV antivirals could offer a viable treatment strategy for COVID-19.