New Candidates for Furin Inhibition as Probable Treat for COVID-19: Docking Output

TL;DR

This study identifies potential furin inhibitors, including certain antiviral and antibiotic drugs, through docking experiments, suggesting they could serve as treatments or prophylactics for COVID-19 by targeting the virus activation process.

Contribution

The paper presents docking-based screening of approved drugs targeting furin, proposing new candidates for COVID-19 treatment and prophylaxis based on binding affinity.

Findings

Saquinavir, nelfinavir, and atazanavir show high affinity as furin inhibitors.

Clarithromycin, niclosamide, and erythromycin may serve as prophylactic agents.

Proposed drugs could be used as adjuvant therapy or prophylaxis in COVID-19.

Abstract

Furin is a serine protease that takes part in the processing and activation of the host cell pre-proteins. The enzyme also plays an important role in the activation of several viruses like the newly emerging SARS-CoV-2 virus that causes COVID-19 disease with a high rate of virulence and mortality. Unlike viral enzymes, furin owns a constant sequence and active site characteristics and seems to be a better target for drug design for COVID-19 treatment. Considering furin active site as receptor and some approved drugs from different classes including antiviral, antibiotics, and anti protozoa/anti parasites with suspected beneficial effects on COVID-19, as ligands we have carried out docking experiments in HEX software to pickup those capable to bind furin active site with high affinity and suggest them as probable candidates for clinical trials assessments. Our docking experiments show that saquinavir, nelfinavir, and atazanavir with cumulative inhibitory effects of 2.52, 2.16, and 2.13 respectively seem to be the best candidates for furin inhibition even in severe cases of COVID-19 as adjuvant therapy, while clarithromycin, niclosamide, and erythromycin with cumulative inhibitory indices of 1.97, 1.90, and 1.84 respectively with lower side effects than antiviral drugs could be suggested as prophylaxes for the first stage of COVID-19 as a promising treat.