New Tetramic Acid Derivatives From the Deep-Sea-Derived Fungus Penicillium sp. SCSIO06868 With SARS-CoV-2 Mpro Inhibitory Activity Evaluation.

Xiaoyan Pang,Bin Yang,Xin Wang,Weihao Chen,Shihai Xu,Xuefeng Zhou,Junfeng Wang,Xinpeng Tian,Yonghong Liu

doi:10.3389/fmicb.2021.730807

Abstract

Three new tetramic acid derivatives (1–3) and a new polyketide (4) along with eight known compounds (5–12) were isolated from cultures of the deep-sea-derived fungus Penicillium sp. SCSIO06868. Four new structures were elucidated by analysis of one-dimensional/two-dimensional nuclear magnetic resonance (NMR) data and high-resolution electrospray ionization mass spectrometry. Their absolute configurations were established by X-ray crystallography analysis and comparison of the experimental and reported electronic circular dichroism (ECD) values or specific optical rotation. Compound 3 exhibited potent, selective inhibitory activities against Staphylococcus aureus and methicillin-resistant S. aureus with minimum inhibitory concentration values of both 2.5 μg/ml. Also, compound 3 showed weak antiviral activity against severe acute respiratory syndrome coronavirus 2 main protease, which was responsible for the coronavirus disease 2019 pandemic.

Highlights

Natural products bearing a tetramic acid structural fragment are isolated from various terrestrial and marine organisms, such as bacteria, cyanobacteria, fungi, and sponges (Mo et al, 2014; Jiang et al, 2020)
Compound 3 showed weak inhibitory activity against Mpro enzyme, which was responsible for the COVID-19 pandemic
The absolute configurations of new compounds were established by X-ray crystallography analysis and comparison of the experimental and reported electronic circular dichroism (ECD) value or specific optical rotation

Summary

Introduction

Natural products bearing a tetramic acid structural fragment (pyrrolidine-2,4-dione) are isolated from various terrestrial and marine organisms, such as bacteria, cyanobacteria, fungi, and sponges (Mo et al, 2014; Jiang et al, 2020). Tetramic Acids Targeting SARS-CoV-2 Mpro for bioprospecting (Jin et al, 2016; Pang et al, 2020). As part of our ongoing research for bioactive secondary metabolites from deep-sea-derived fungi (Chen et al, 2016; Wang et al, 2016; Pang et al, 2021), the fungus Penicillium sp. Three new tetramic acid derivatives (1–3) and a new polyketide (4) along with eight known compounds (5– 12) (Figure 1) were isolated from the deep-sea-derived fungus Penicillium sp. All isolated compounds (1–12) were tested for their antiviral activities against SARS-CoV-2 Mpro in vitro. Molecular docking research was performed to mimic the interactions between the bioactive compound and SARS-CoV-2 Mpro. We described the isolation, structure elucidation, and bioactivity evaluation of the 12 compounds

Methods

Results

Conclusion