Article Alert: Natural Compounds with Broad Antiviral Activity against SARS-CoV-2 VOCs

The COVID-19 pandemic continues to be a global public health crisis and emerging variants of concern (VOCs), particularly Omicron subvariants, have progressively eroded the clinical utility of therapeutic monoclonal antibodies. Thus, the search for novel antiviral agents with efficacy against a spectrum of existing and evolving SARS-CoV-2 lineages remains a major focus of research.

A new study by Pérez-Vargas et al. conducted a cell-based high-content screening of 373 natural products (NPs) from plants, fungi, bacteria, and even marine sponges to identify pan-SARS-CoV-2 antiviral agents (1). Among the more than 70 promising candidates demonstrating anti-SARS-CoV-2 activity, 26 had half-maximal effective concentrations (EC₅₀) below 50 μM. The authors discovered that three of these (i.e., holyrine A, alotaketal C (a protein kinase C (PKC) activator), and bafilomycin D (a V-ATPase inhibitor)) were effective at nanomolar concentrations against Omicron subvariants BA.5, BA.2, and BA.1 as well as the Delta VOC. Alotaketal C and bafilomycin D both appear to function as host-directed antivirals, and their respective known activities suggest that additional research into the roles of PKC and human V-ATPase in SARS-CoV-2 infection and the viral lifecycle are indicated. The intriguing findings of this work could direct the development of novel pan-SARS-CoV-2 drugs.

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Reference:

1. Antiviral Res. 2023 Jan;209:105484. doi: 10.1016/j.antiviral.2022.105484. Epub 2022 Dec 8.