Abstract
Angiotensin converting enzyme 2 (ACE2) (EC:3.4.17.23) is a transmembrane protein which is considered as a receptor for spike protein binding of novel coronavirus (SARS-CoV2). Since no specific medication is available to treat COVID-19, designing of new drug is important and essential. In this regard, in silico method plays an important role, as it is rapid and cost effective compared to the trial and error methods using experimental studies. Natural products are safe and easily available to treat coronavirus affected patients, in the present alarming situation. In this paper five phytochemicals, which belong to flavonoid and anthraquinone subclass, have been selected as small molecules in molecular docking study of spike protein of SARS-CoV2 with its human receptor ACE2 molecule. Their molecular binding sites on spike protein bound structure with its receptor have been analyzed. From this analysis, hesperidin, emodin and chrysin are selected as competent natural products from both Indian and Chinese medicinal plants, to treat COVID-19. Among them, the phytochemical hesperidin can bind with ACE2 protein and bound structure of ACE2 protein and spike protein of SARS-CoV2 noncompetitively. The binding sites of ACE2 protein for spike protein and hesperidin, are located in different parts of ACE2 protein. Ligand spike protein causes conformational change in three-dimensional structure of protein ACE2, which is confirmed by molecular docking and molecular dynamics studies. This compound modulates the binding energy of bound structure of ACE2 and spike protein. This result indicates that due to presence of hesperidin, the bound structure of ACE2 and spike protein fragment becomes unstable. As a result, this natural product can impart antiviral activity in SARS CoV2 infection. The antiviral activity of these five natural compounds are further experimentally validated with QSAR study.
Highlights
Angiotensin converting enzyme 2 (ACE2) (EC:3.4.17.23) is a transmembrane protein which is considered as a receptor for spike protein binding of novel coronavirus (SARS-CoV2)
Receptor Binding Domain (RBD) of spike glycoprotein interacts with ACE2 receptor in Protease Domain (PD) of the host human cell, causing viral infection
Tai et al.[3] suggested that RBD fragment in SARS-CoV-2 strongly binds with human ACE2 as well as bat ACE2 receptors
Summary
Angiotensin converting enzyme 2 (ACE2) (EC:3.4.17.23) is a transmembrane protein which is considered as a receptor for spike protein binding of novel coronavirus (SARS-CoV2). In this paper five phytochemicals, which belong to flavonoid and anthraquinone subclass, have been selected as small molecules in molecular docking study of spike protein of SARS-CoV2 with its human receptor ACE2 molecule Their molecular binding sites on spike protein bound structure with its receptor have been analyzed. The molecular level structure of SARS-CoV-2 spike protein has a Receptor Binding Domain (RBD) for binding to host human cells. Spike (S) protein is the most vital protein which controls the biological processes such as viral particle attachment, fusion and lastly entry in the host cell As a result, it can be considered as a target for development of medicines in COVID-19, as well as SARS-CoV infection[4,5]. SARS-CoV-2 spike protein is about 10–20 times more probable to bind with ACE2 on human cells, compared to that of spike protein from the SARS-CoV infection (occurred in 2002)
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