New Anti-Viral Approach for Treating COVID-19 Identified

Posted On October 21, 2020     

The research done at the University of Hongkong has discovered a novel antiviral strategy for the treatment of COVID-19. The metallodrugs utilized in treating infectious diseases show effectiveness in repressing SARS-CoV-2 replication and ease viral-associated symptoms in an animal model.The discovery provides a novel and readily available therapeutic alternative with a high clinical perspective for infection with SARS-CoV-2. This innovative work has been published online in a famous scientific journal Nature Microbiology. An associated patent has been filed in the US.

SARS-CoV-2 is a rising coronavirus that has caused around 30 million laboratory-confirmed cases and more than 1 million deaths worldwide, seeing as December 2019.As the procedure of developing an effective vaccine is still continuing, another approach for treatment and prevention of the disease is to recognize anti-COVID-19 agents from existing virus-specific antiviral drugs to reprocess their uses and target the new virus.

A broad-spectrum antiviral drug, Remdesivir, has been reported to show success towards SARS-CoV-2. Nevertheless, the global shortage of the drug, its moderately high price, and the absence of significant clinical advantages in severe cases, are factors that have restricted its extensive applications.

Clinical trials on a sequence of antiviral agents are continuing, which have yet to reveal therapeutic efficacies. Consequently, more significant efforts are required to expand the evaluation to cover a broader spectrum of clinically accepted drugs.

Study method and findings

Usually, metal compounds are used as anti-microbial agents. The research team recognized ranitidine bismuth citrate (RBC), a frequently used anti-ulcer drug. It contains metal Bismuth used as a potent anti-SARS-CoV-2 agent, both in vitro and in vivo, to treat Helicobacter pylori-associated infection.

RBC targets the crucial non-structural protein 13 (Nsp13), a viral helicase necessary for SARS-CoV-2 to imitate, by displacing the critical zinc(II) ions in the zinc-binding with Bismuth-ions, to potently suppress the activity of the helicase.RBC can decrease viral loads by over 1,000-folds in SARS-CoV-2-infected cells. In a golden Syrian hamster model, RBC subdues SARS-CoV-2 duplication to decrease viral loads by ~100 folds in both the lower and upper respiratory tracts and alleviate virus-associated pneumonia.

The team explored the mechanisms of RBC on SARS-CoV-2 and exposed for the first time the vital Nsp13 helicase as a druggable target by RBC. It irrevocably kicks out the crucial zinc(II) ions in the zinc-binding area to modify it to bismuth-bound through a distinct metal displacement route.

The findings emphasize viral helicases as a druggable target and the high clinical possibility of bismuth(III) drugs and other metallodrugs for medicating SARS-CoV-2 infections.

Optimistically, more antiviral agents from readily obtainable clinically approved drugs could be recognized for the potential treatment of COVID-19 infections.
 
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