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      Potential Role of Peptide-Based Antiviral Therapy Against SARS-CoV-2 Infection

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          Abstract

          Because of the uninterrupted spread of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectious disease (COVID-19) with substantial illness and mortality rates, there is an urgent requirement of suitable antiviral agent/therapy to control this pandemic, but not yet established. The primary cause of SARS-CoV-2 infection is the crosstalk between the SARS-CoV-2 and host surface receptor protein, human angiotensin-converting enzyme 2 (hACE2), prior to cellular entry. Hence, blocking at the initial stage of virus entry could be a promising strategy/therapy to combat the SARS-CoV-2 infection. Many drugs as SARS-CoV-2 blocker have been proposed. Among them, peptide-based antivirals are one. This Viewpoint discusses the potential antiviral role and feasibility of two classes of peptides for prevention of SARS-CoV-2 infection, where (1) a designed peptide (replication of virus binding domain of hACE2), and (2) antimicrobial peptides (AMPs; natural and first line host defense peptide), both may reduce virus load into the host cell by blocking cellular surface receptors and/or disruption of virus cell membrane at the stage of virus entry. These finding may provide a novel antiviral therapy against COVID-19, which might control the current global health crisis.

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          Most cited references14

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          Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia

          Abstract Background The initial cases of novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, Hubei Province, China, in December 2019 and January 2020. We analyzed data on the first 425 confirmed cases in Wuhan to determine the epidemiologic characteristics of NCIP. Methods We collected information on demographic characteristics, exposure history, and illness timelines of laboratory-confirmed cases of NCIP that had been reported by January 22, 2020. We described characteristics of the cases and estimated the key epidemiologic time-delay distributions. In the early period of exponential growth, we estimated the epidemic doubling time and the basic reproductive number. Results Among the first 425 patients with confirmed NCIP, the median age was 59 years and 56% were male. The majority of cases (55%) with onset before January 1, 2020, were linked to the Huanan Seafood Wholesale Market, as compared with 8.6% of the subsequent cases. The mean incubation period was 5.2 days (95% confidence interval [CI], 4.1 to 7.0), with the 95th percentile of the distribution at 12.5 days. In its early stages, the epidemic doubled in size every 7.4 days. With a mean serial interval of 7.5 days (95% CI, 5.3 to 19), the basic reproductive number was estimated to be 2.2 (95% CI, 1.4 to 3.9). Conclusions On the basis of this information, there is evidence that human-to-human transmission has occurred among close contacts since the middle of December 2019. Considerable efforts to reduce transmission will be required to control outbreaks if similar dynamics apply elsewhere. Measures to prevent or reduce transmission should be implemented in populations at risk. (Funded by the Ministry of Science and Technology of China and others.)
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            Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor

            A new and highly pathogenic coronavirus (severe acute respiratory syndrome coronavirus-2, SARS-CoV-2) caused an outbreak in Wuhan city, Hubei province, China, starting from December 2019 that quickly spread nationwide and to other countries around the world1-3. Here, to better understand the initial step of infection at an atomic level, we determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 bound to the cell receptor ACE2. The overall ACE2-binding mode of the SARS-CoV-2 RBD is nearly identical to that of the SARS-CoV RBD, which also uses ACE2 as the cell receptor4. Structural analysis identified residues in the SARS-CoV-2 RBD that are essential for ACE2 binding, the majority of which either are highly conserved or share similar side chain properties with those in the SARS-CoV RBD. Such similarity in structure and sequence strongly indicate convergent evolution between the SARS-CoV-2 and SARS-CoV RBDs for improved binding to ACE2, although SARS-CoV-2 does not cluster within SARS and SARS-related coronaviruses1-3,5. The epitopes of two SARS-CoV antibodies that target the RBD are also analysed for binding to the SARS-CoV-2 RBD, providing insights into the future identification of cross-reactive antibodies.
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              A SARS-CoV-2 Protein Interaction Map Reveals Targets for Drug-Repurposing

              SUMMARY The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 2.3 million people, killed over 160,000, and caused worldwide social and economic disruption 1,2 . There are currently no antiviral drugs with proven clinical efficacy, nor are there vaccines for its prevention, and these efforts are hampered by limited knowledge of the molecular details of SARS-CoV-2 infection. To address this, we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), identifying 332 high-confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (29 FDA-approved drugs, 12 drugs in clinical trials, and 28 preclinical compounds). Screening a subset of these in multiple viral assays identified two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the Sigma1 and Sigma2 receptors. Further studies of these host factor targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19.
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                Author and article information

                Journal
                ACS Pharmacol Transl Sci
                ACS Pharmacol Transl Sci
                pt
                aptsfn
                ACS Pharmacology & Translational Science
                American Chemical Society
                2575-9108
                24 July 2020
                : acsptsci.0c00081
                Affiliations
                [1]National Institute of Technology Sikkim , Ravangla Campus, Barfung Block, Ravangla Sub Division, South Sikkim 737139, India
                Author notes
                Article
                10.1021/acsptsci.0c00081
                7393772
                32821885
                43a1e0e6-3862-4d9c-9d78-fe6542456e4f
                Copyright © 2020 American Chemical Society

                This article is made available via the PMC Open Access Subset 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 the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 09 July 2020
                Categories
                Viewpoint
                Custom metadata
                pt0c00081
                pt0c00081

                covid-19,hace2,virus-host interaction,peptides,antiviral therapy

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