Abstract
Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is a positive-strand RNA virus that causes severe respiratory syndrome in humans, which is now referred to as coronavirus disease 2019 (COVID-19). Since December 2019, the new pathogen has rapidly spread globally, with over 65 million cases reported to the beginning of December 2020, including over 1.5 million deaths. Unfortunately, currently, there is no specific and effective treatment for COVID-19. As SARS-CoV-2 relies on its spike proteins (S) to bind to a host cell-surface receptor angiotensin-converting enzyme-2(ACE2), and this interaction is proved to be responsible for entering a virus into host cells, it makes an ideal target for antiviral drug development. In this work, we design three very short peptides based on the ACE2 sequence/structure fragments, which may effectively bind to the receptor-binding domain (RBD) of S protein and may, in turn, disrupt the important virus-host protein–protein interactions, blocking early steps of SARS-CoV-2 infection. Two of our peptides bind to virus protein with affinity in nanomolar range, and as very short peptides have great potential for drug development.
Highlights
IntroductionBased on the genome sequence analysis, the new SARS-CoV-2 shows strong homology (over 79% of sequence identity) with another positive-sense, single-stranded RNA virus, severe acute respiratory syndrome-related coronavirus (SARS-CoV) [4], which was responsible for a global outbreak in 2003 [5]
Accepted: 7 April 2021Infection caused by novel severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) is referred to as COVID-19 [1], and has become a global health problem within the first three months since its earliest incidence, noticed in December 2019 in China [2].One year later, at the beginning of December 2020, SARS-CoV-2 had infected over 65 million individuals worldwide and is responsible for over 1.5 million deaths [3].Based on the genome sequence analysis, the new SARS-CoV-2 shows strong homology with another positive-sense, single-stranded RNA virus, severe acute respiratory syndrome-related coronavirus (SARS-CoV) [4], which was responsible for a global outbreak in 2003 [5]
After visual inspection of the protein–protein complex, we focused our research on region 1, as it is located in the central part of the interface, with the single continuous sequence fragment containing the well-defined α-helical secondary structure, and creates mainly polar interactions (Figure 2) with S protein
Summary
Based on the genome sequence analysis, the new SARS-CoV-2 shows strong homology (over 79% of sequence identity) with another positive-sense, single-stranded RNA virus, severe acute respiratory syndrome-related coronavirus (SARS-CoV) [4], which was responsible for a global outbreak in 2003 [5]. This strong similarity quickly suggested that both viruses may share the same host cell receptor [4], which for SARS-CoV was well defined as angiotensin-converting enzyme-2 (ACE2) [6]. This process is mediated by the receptor-binding domain (RBD) of the virus spike (S) glycoprotein [8], which directly interacts with human
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