The rampageous transmission of SARS-CoV-2 has been devastatingly impacting human life
and public health since late 2019. The waves of pandemic events caused by distinct
coronaviruses at present and over the past decades have prompted the need to develop
broad-spectrum antiviral drugs against them. In this study, our Pentarlandir ultrapure
and potent tannic acids (UPPTA) showed activities against two coronaviral strains,
SARS-CoV-2 and HCoV-OC43, the earliest-known coronaviruses. The mode of inhibition of
Pentarlandir UPPTA is likely to act on 3-chymotrypsin-like protease (3CLpro) to prevent
viral replication, as supported by results of biochemical analysis, a 3CLpro assay, and
a “gain-of-function” 3CLpro overexpressed cell-based method. Even in the
3CLpro overexpressed environment, Pentarlandir UPPTA remained its antiviral
characteristic. Utilizing cell-based virucidal and cytotoxicity assays, the 50%
effective concentrations (EC
50
) and 50% cytotoxicity concentration
(CC
50
) of Pentarlandir UPPTA were determined to be ∼0.5 and 52.5
μM against SARS-CoV-2, while they were 1.3 and 205.9 μM against HCoV-OC43,
respectively. In the pharmacokinetic studies, Pentarlandir UPPTA was distributable at a
high level to the lung tissue with no accumulation in the body, although the
distribution was affected by the food effect. With further investigation in toxicology,
Pentarlandir UPPTA demonstrated an overall safe toxicology profile. Taking these
findings together, Pentarlandir UPPTA is considered to be a safe and efficacious
pancoronal antiviral drug candidate that has been advanced to clinical development.
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