A New Antiviral Strategy Was Discovered For Treating COVID-19

CHANGSHA, China - Oct. 21, 2020 - PRLog -- A research team led by Professor Hongzhe SUN, Norman & Cecilia Yip Professor in Bioinorganic Chemistry, has discovered a novel antiviral strategy for treatment of COVID-19.

They discovered that a class of metallodrugs currently used in the treatment of other infectious diseases is showing efficacy to potently suppress SARS-CoV-2 replication and relieve viral-associated symptoms in an animal model. The findings provide a new and readily available therapeutic option with high clinical potential for infection with SARS-CoV-2.

Generally, metal compounds are used as anti-microbial agents; their antiviral activities have rarely been explored. After screening a series of metallodrugs and related compounds, the research team identified ranitidine bismuth citrate (RBC), a commonly used anti-ulcer drug which contains the metal Bismuth for treatment of Helicobacter pylori-associated infection, as a potent anti-SARS-CoV-2 agent, both in vitro and in vivo.

RBC targets the vital non-structural protein 13 (Nsp13), a viral helicase essential for SARS-CoV-2 to replicate, by displacing the crucial zinc(II) ions in the zinc-binding with Bismuth-ions, to potently suppress the activity of the helicase.

RBC has been demonstrated to greatly reduce viral loads by over 1,000-folds in SARS-CoV-2-infected cells.
RBC remarkably diminishes the level of prognostic markers and other major pro-inflammatory cytokines and chemokines in severe COVID-19 cases of infected hamsters, compared to the Remdesivir-treated group and control group.

RBC exhibits a low cytotoxicity with a high selectivity index at 975 (the larger the number the safer the drug), as compared to Remdesivir which has a low selectivity index at 129. The finding indicates a wide window between the drug's cytotoxicity and antiviral activity, which allows a great flexibility in adjusting its dosages for treatment.

The team investigated the mechanisms of RBC on SARS-CoV-2 and revealed for the first time the vital Nsp13 helicase as a druggable target by RBC. It irreversibly kicks out the crucial zinc(II) ions in the zinc-binding domain to change it to bismuth-bound via a distinct metal displacement route.

The research findings highlight viral helicases as a druggable target, and the high clinical potential of bismuth(III) drugs and other metallodrugs for treatment of SARS-CoV-2 infections.

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