Natural Bioactive Compounds from Fungi as Potential Candidates for Protease Inhibitors and Immunomodulators to Apply for Coronaviruses.

Nakarin Suwannarach,Thanawat Pattananandecha,Jaturong Kumla,Saisamorn Lumyong,Kanaporn Sujarit,Chalermpong Saenjum

doi:10.3390/molecules25081800

Abstract

The inhibition of viral protease is an important target in antiviral drug discovery and development. To date, protease inhibitor drugs, especially HIV-1 protease inhibitors, have been available for human clinical use in the treatment of coronaviruses. However, these drugs can have adverse side effects and they can become ineffective due to eventual drug resistance. Thus, the search for natural bioactive compounds that were obtained from bio-resources that exert inhibitory capabilities against HIV-1 protease activity is of great interest. Fungi are a source of natural bioactive compounds that offer therapeutic potential in the prevention of viral diseases and for the improvement of human immunomodulation. Here, we made a brief review of the current findings on fungi as producers of protease inhibitors and studies on the relevant candidate fungal bioactive compounds that can offer immunomodulatory activities as potential therapeutic agents of coronaviruses in the future.

Highlights

Coronaviruses (CoVs) are a large group of enveloped viruses with non-segmented, single-strand, and positive-sense RNA genomes
A clinical study of 41 patients infected with SARS-CoV-2 in Wuhan, China showed that 63% of the patients had lymphopenia, 12% had acute respiratory distress syndrome (ARDS), all patients had pneumonia, and the intensive care patients reported higher plasma levels of IL-2, IL-7, IL-10, GSCF, IP10, MCP1, MIP1A, and tumor necrosis factor-alpha (TNF)-α than the non-intensive care patients [108]
The discovery and production of antiviral metabolites from fungi have emerged as part of an exciting field in viral therapeutic and antiviral drug development

Summary

Introduction

Coronaviruses (CoVs) are a large group of enveloped viruses with non-segmented, single-strand, and positive-sense RNA genomes. The mortality rate of SARS-CoV-2 infection has been seen to be around two percent in China, which is much less than the mortality rates of SARS-CoV and MERS-CoV infection [5] It has caused global concern by its efficient human-to-human transmission, leading to its widespread outbreak in many countries around the world [4,5,6]. Clinical practice guidelines and the treatment protocols of WHO and the Center for Disease Control and Prevention (CDC) for a patient infected with SARS-CoV-2 are similar to those of other viral causes of pneumonia These include prompt supportive care, like oxygen therapy, fluid management, empiric antimicrobials (in case of sepsis), and others [5]

Protease Inhibitor Drugs for CoVs

HIV-1 Protease Inhibitors Isolated from Fungi

Potential of Fungal Bioactive Compounds for Immunomodulators

Findings

Conclusions