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      The antiviral and the coronavirus-host protein pathways inhibiting properties of herbs and natural compounds - Additional weapons in the fight against the COVID-19 pandemic?

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          Abstract

          Introduction

          As of March 11th, 2020, the World Health Organization declared the COVID-19 outbreak a pandemic. Articles published after the SARS-CoV-1 (2002) epidemic suggest that the use of an herbal-drug integrative medical approach could have contributed to a lower fatality rate and a more rapid response in controlling the outbreak.

          Methods

          Pubmed was searched for articles that investigated the antiviral properties and mechanisms of action of herbs or natural compounds against the SARS-coronavirus (CoV).

          Results

          Forty-three (43) relevant papers were located. A general count rendered 450+ herbs and natural compounds with antiviral properties against the SARS-CoV and related viruses. From the 43 articles, thirty-one (31) uncovered the mechanisms of action of the natural substances able to oppose the coronavirus.

          Discussion

          A series of herbs and natural compounds demonstrated moderate to strong antiviral activity. Research on many herbs-natural compounds also showed potent and significant inhibition of CoV-host protein pathways responsible for different phases of viral replication specifically targeting 3CL PRO, PL PRO, RdRp, helicase protein, S protein, N protein, 3a protein, Cathepsin L, Nsp1, Nsp3c, and ORF7a, and the S protein-ACE-2 interaction.

          Conclusion

          The herbs-natural compounds with antiviral activity and that caused inhibition/blockade of the CoV-host protein pathways are potential therapeutic candidates. The homology between the SARS-CoV-1 and SARS-CoV-2 is around 80%. Thus, effective herbs-compounds for the former would likely be beneficial for the latter also depending on target protein similarities between the viruses. Here we provide the mechanistic bases supporting an integrative approach that includes natural compounds to fight coronavirus infections.

          Graphical abstract

          Highlights

          • •

            We researched herbs-natural compounds with properties against the SARS-coronavirus (CoV).

          • •

            Approximately 450+ herbs-natural compounds showed strong-moderate antiviral properties.

          • •

            Many herbs potently-significantly inhibited-blocked SARS-CoVs-host protein pathways.

          • •

            These herbs-compounds are potential therapeutic candidates to address the SARS-CoVs.

          • •

            The drug-herbal integrative medical approach could support the conventional medical system.

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          Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding

          Roujian Lu, Xiang Zhao, Juan Li … (2021)
          Summary Background In late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed. Methods We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions determined by rapid amplification of cDNA ends. Phylogenetic analysis of these 2019-nCoV genomes and those of other coronaviruses was used to determine the evolutionary history of the virus and help infer its likely origin. Homology modelling was done to explore the likely receptor-binding properties of the virus. Findings The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues. Interpretation 2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation. Funding National Key Research and Development Program of China, National Major Project for Control and Prevention of Infectious Disease in China, Chinese Academy of Sciences, Shandong First Medical University.
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            Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods

            Canrong Wu, Yang Liu, Yueying Yang … (2020)
            SARS-CoV-2 has caused tens of thousands of infections and more than one thousand deaths. There are currently no registered therapies for treating coronavirus infections. Because of time consuming process of new drug development, drug repositioning may be the only solution to the epidemic of sudden infectious diseases. We systematically analyzed all the proteins encoded by SARS-CoV-2 genes, compared them with proteins from other coronaviruses, predicted their structures, and built 19 structures that could be done by homology modeling. By performing target-based virtual ligand screening, a total of 21 targets (including two human targets) were screened against compound libraries including ZINC drug database and our own database of natural products. Structure and screening results of important targets such as 3-chymotrypsin-like protease (3CLpro), Spike, RNA-dependent RNA polymerase (RdRp), and papain like protease (PLpro) were discussed in detail. In addition, a database of 78 commonly used anti-viral drugs including those currently on the market and undergoing clinical trials for SARS-CoV-2 was constructed. Possible targets of these compounds and potential drugs acting on a certain target were predicted. This study will provide new lead compounds and targets for further in vitro and in vivo studies of SARS-CoV-2, new insights for those drugs currently ongoing clinical studies, and also possible new strategies for drug repositioning to treat SARS-CoV-2 infections.
            Article 0 comments Cited 989 times – based on 0 reviews     Review now
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              Coronavirus infections and immune responses

              Geng Li, Yaohua Fan, Yanni Lai … (2020)
              Abstract Coronaviruses (CoVs) are by far the largest group of known positive‐sense RNA viruses having an extensive range of natural hosts. In the past few decades, newly evolved Coronaviruses have posed a global threat to public health. The immune response is essential to control and eliminate CoV infections, however, maladjusted immune responses may result in immunopathology and impaired pulmonary gas exchange. Gaining a deeper understanding of the interaction between Coronaviruses and the innate immune systems of the hosts may shed light on the development and persistence of inflammation in the lungs and hopefully can reduce the risk of lung inflammation caused by CoVs. In this review, we provide an update on CoV infections and relevant diseases, particularly the host defense against CoV‐induced inflammation of lung tissue, as well as the role of the innate immune system in the pathogenesis and clinical treatment.
              Article 0 comments Cited 864 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Andréa D. Fuzimoto
                Journal
                Journal ID (nlm-ta): J Tradit Complement Med
                Journal ID (iso-abbrev): J Tradit Complement Med
                Title: Journal of Traditional and Complementary Medicine
                Publisher: Center for Food and Biomolecules, National Taiwan University. Production and hosting by Elsevier Taiwan LLC.
                ISSN (Electronic): 2225-4110
                Publication date PMC-release: 30 May 2020
                Publication date (Electronic): 30 May 2020
                Affiliations
                [a ]Holistic Sync - Holistic Integrative Medicine, DAOM, Brazil
                [b ]Dipartimento di Scienze della Salute, Università“A. Avogadro”, Italy
                Author notes
                [∗ ]Corresponding author. Holistic Sync - Holistic Integrative Medicine, R. Dona Mariana 36, Botafogo, Rio de Janeiro, RJ, 22280-020, Brazil. anfuzimoto@ 123456fivebranches.edu
                Article
                Publisher ID: S2225-4110(20)30478-8
                DOI: 10.1016/j.jtcme.2020.05.003
                PMC ID: 7260130
                PubMed ID: 32691005
                SO-VID: 1e400184-7202-49a2-959f-e3e9b31d35fb
                Copyright © © 2020 Center for Food and Biomolecules, National Taiwan University. Production and hosting by Elsevier Taiwan LLC.
                License:

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                Date received : 20 April 2020
                Date revision received : 21 May 2020
                Date accepted : 26 May 2020
                Categories
                Subject: Article

                Keywords: coronavirus,covid-19,herbs,natural compounds,antiviral,pandemic
                Data availability:
                Keywords: coronavirus, covid-19, herbs, natural compounds, antiviral, pandemic

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