Abstract
In this review, we reveal the latest developments at the interface between SARS-CoV-2 and the host cell surface. In particular, we evaluate the current and potential mechanisms of binding, fusion and the conformational changes of the spike (S) protein to host cell surface receptors, especially the human angiotensin-converting enzyme 2 (ACE2) receptor. For instance, upon the initial attachment, the receptor binding domain of the S protein forms primarily hydrogen bonds with the protease domain of ACE2 resulting in conformational changes within the secondary structure. These surface interactions are of paramount importance and have been therapeutically exploited for antiviral design, such as monoclonal antibodies. Additionally, we provide an insight into novel therapies that target viral non-structural proteins, such as viral RNA polymerase. An example of which is remdesivir which has now been approved for use in COVID-19 patients by the US Food and Drug Administration. Establishing further understanding of the molecular details at the cell surface will undoubtably aid the development of more efficacious and selectively targeted therapies to reduce the burden of COVID-19.
Highlights
Coronavirus disease 2019 (COVID-19) is caused by a novel strain of coronavirus (CoV), termed severe acute respiratory syndrome (SARS)-CoV-2
We explore SARS-CoV-2–host cell surface interactions, the cellular entry mechanisms, potential therapies and allude to why SARS-CoV-2 has developed pandemic potential when compared with other coronaviruses
In the process of the receptor binding domain (RBD) transitioning into the open conformation, molecular interactions from the S1 domain with a segment that precedes the S2 fusion protein (FP) region are lost; it is hypothesized that this primes the S protein for helical rearrangements of S2 domain required for viral and host cell membrane fusion [29,36]
Summary
Coronavirus disease 2019 (COVID-19) is caused by a novel strain of coronavirus (CoV), termed severe acute respiratory syndrome (SARS)-CoV-2. SARS-CoV-2 has infected more than 118 million people worldwide resulting in 2.6 million deaths. SARS-CoV-1 affected 8422 people and caused 916 deaths (mortality rate 11%) before being contained [3]. Entry into the host cell is a crucial and necessary step in the life cycle of the virus. Allows the virus to enter, establish an infection and replicate, which can lead to tissue damage and death in some cases. Due to this similarity, much of the understanding of SARS-CoV-2 molecular interactions, proteins and pathogenesis has been based on research in other coronaviruses, especially SARS-CoV-1. We explore SARS-CoV-2–host cell surface interactions, the cellular entry mechanisms, potential therapies and allude to why SARS-CoV-2 has developed pandemic potential when compared with other coronaviruses
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