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      Metal-based strategies for the fight against COVID-19

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          Abstract

          Metallodrugs and metal complexes kill SARS-CoV-2 through inhibition of multiple viral proteins/enzymes.

          Abstract

          The emerging COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has claimed over six million lives globally to date. Despite the availability of vaccines, the pandemic still cannot be fully controlled owing to rapid mutation of the virus that renders enhanced transmissibility and antibody evasion. This is thus an unmet need to develop safe and effective therapeutic options for COVID-19, in particular, remedies that can be used at home. Considering the great success of multi-targeted cocktail therapy for the treatment of viral infections, metal-based drugs might represent a unique and new source of antivirals that resemble a cocktail therapy in terms of their mode of actions. In this review, we first summarize the role that metal ions played in SARS-CoV-2 viral replication and pathogenesis, then highlight the chemistry of metal-based strategies in the fight against SARS-CoV-2 infection, including both metal displacement and chelation based approaches. Finally, we outline a perspective and direction on how to design and develop metal-based antivirals for the fight against the current or future coronavirus pandemic.

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          A pneumonia outbreak associated with a new coronavirus of probable bat origin

          Peng Zhou, Xing-Lou Yang, Xian-Guang Wang … (2020)
          Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats 1–4 . Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans 5–7 . Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.
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            A new coronavirus associated with human respiratory disease in China

            Fan Wu, Su Zhao, Bin Yu … (2020)
            Emerging infectious diseases, such as severe acute respiratory syndrome (SARS) and Zika virus disease, present a major threat to public health 1–3 . Despite intense research efforts, how, when and where new diseases appear are still a source of considerable uncertainty. A severe respiratory disease was recently reported in Wuhan, Hubei province, China. As of 25 January 2020, at least 1,975 cases had been reported since the first patient was hospitalized on 12 December 2019. Epidemiological investigations have suggested that the outbreak was associated with a seafood market in Wuhan. Here we study a single patient who was a worker at the market and who was admitted to the Central Hospital of Wuhan on 26 December 2019 while experiencing a severe respiratory syndrome that included fever, dizziness and a cough. Metagenomic RNA sequencing 4 of a sample of bronchoalveolar lavage fluid from the patient identified a new RNA virus strain from the family Coronaviridae, which is designated here ‘WH-Human 1’ coronavirus (and has also been referred to as ‘2019-nCoV’). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) that had previously been found in bats in China 5 . This outbreak highlights the ongoing ability of viral spill-over from animals to cause severe disease in humans.
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              Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein

              Alexandra C Walls, Young-Jun Park, M. Alejandra Tortorici … (2020)
              Summary The emergence of SARS-CoV-2 has resulted in >90,000 infections and >3,000 deaths. Coronavirus spike (S) glycoproteins promote entry into cells and are the main target of antibodies. We show that SARS-CoV-2 S uses ACE2 to enter cells and that the receptor-binding domains of SARS-CoV-2 S and SARS-CoV S bind with similar affinities to human ACE2, correlating with the efficient spread of SARS-CoV-2 among humans. We found that the SARS-CoV-2 S glycoprotein harbors a furin cleavage site at the boundary between the S1/S2 subunits, which is processed during biogenesis and sets this virus apart from SARS-CoV and SARS-related CoVs. We determined cryo-EM structures of the SARS-CoV-2 S ectodomain trimer, providing a blueprint for the design of vaccines and inhibitors of viral entry. Finally, we demonstrate that SARS-CoV S murine polyclonal antibodies potently inhibited SARS-CoV-2 S mediated entry into cells, indicating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination.
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                Author and article information

                Contributors
                Journal
                Journal ID (publisher-id): CHCOFS
                Title: Chemical Communications
                Abbreviated Title: Chem. Commun.
                Publisher: Royal Society of Chemistry (RSC)
                ISSN (Print): 1359-7345
                ISSN (Electronic): 1364-548X
                Publication date Created: July 05 2022
                Publication date (Electronic): 2022
                Volume: 58
                Issue: 54
                Pages: 7466-7482
                Affiliations
                [1 ]Department of Chemistry, State Key Laboratory of Synthetic Chemistry and CAS-HKU Joint Laboratory of Metallomics on Health and Environment, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
                [2 ]Department of Microbiology and State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
                Article
                DOI: 10.1039/D2CC01772E
                PubMed ID: 35730442
                SO-VID: d3e420ac-a669-458b-afa3-c7b20448f957
                Copyright © © 2022
                License:

                http://rsc.li/journals-terms-of-use

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