Turning the Tide: Natural Products and Natural-Product-Inspired Chemicals as Potential Counters to SARS-CoV-2 Infection

Zhonglei Wang, Liyan Yang, Zhonglei Wang, Liyan Yang

Abstract

The novel and highly pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has become a continued focus of global attention due to the serious threat it poses to public health. There are no specific drugs available to combat SARS-CoV-2 infection. Natural products (carolacton, homoharringtonine, emetine, and cepharanthine) and natural product-inspired small molecules (ivermectin, GS-5734, EIDD-2801, and ebselen) are potential anti-SARS-CoV-2 agents that have attracted significant attention due to their broad-spectrum antiviral activities. Here, we review the research on potential landmark anti-SARS-CoV-2 agents, systematically discussing the importance of natural products and natural-product-inspired small molecules in the research and development of safe and effective antiviral agents.

Keywords: COVID-19; SARS-Cov-2; natural products; natural-product-inspired; potential anti-SARSCoV-2 agents.

Copyright © 2020 Wang and Yang.

Figures

Figure 1
Figure 1
Promising natural products for treating COVID-19. (A) Carolacton was isolated from the myxobacterium Sorangium cellulosum. (B) Homoharringtonine was isolated from the plant Cephalotaxus harringtonii. (C) Emetine was isolated from the plant Psychotria ipecacuanha.
Figure 2
Figure 2
Key strategies in the synthesis of carolacton and homoharringtonine. (A) Synthetic strategies of carolacton by Kirschning’s group, Phillips’s group and Goswami’s group, respectively. (B) Synthetic strategies of homoharringtonine by Gin’s group and Beaudry’s group, respectively.
Figure 3
Figure 3
Promising natural product cepharanthine for treating COVID-19 (image reproduced from ref. 38, bioRxiv, doi: 10.1101/2020.04.14.039925).
Figure 4
Figure 4
Promising natural-product-inspired ivermectin for treating COVID-19.
Figure 5
Figure 5
Promising natural-product-inspired GS-5734 for treating COVID-19 (image reproduced with permission from ref. 54, Acta Pharm. Sin. B, 2020, 10, 766-788).
Figure 6
Figure 6
Gram-scale synthesis of GS-5734.
Figure 7
Figure 7
Promising natural-product-inspired EIDD-2801 for treating COVID-19.
Figure 8
Figure 8
Gram-scale synthesis of EIDD-2801.
Figure 9
Figure 9
Other small molecules for treating COVID-19. (A) Unsuccessful attempt of lopinavir and ritonavir to treat COVID-19. (B) Regulators split on chloroquine and hydroxychloroquine to treat COVID-19.

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