Abstract
Coronaviruses (CoVs) are a group of enveloped positive-sense RNA viruses and can cause deadly diseases in animals and humans. Cell entry is the first and essential step of successful virus infection and can be divided into two ongoing steps: cell binding and membrane fusion. Over the past two decades, stimulated by the global outbreak of SARS-CoV and pandemic of SARS-CoV-2, numerous efforts have been made in the CoV research. As a result, significant progress has been achieved in our understanding of the cell entry process. Here, we review the current knowledge of this essential process, including the viral and host components involved in cell binding and membrane fusion, molecular mechanisms of their interactions, and the sites of virus entry. We highlight the recent findings of host restriction factors that inhibit CoVs entry. This knowledge not only enhances our understanding of the cell entry process, pathogenesis, tissue tropism, host range, and interspecies-transmission of CoVs but also provides a theoretical basis to design effective preventive and therapeutic strategies to control CoVs infection.
Highlights
We primarily focus on the cell entry of coronaviruses infecting economically significant animals and pets, including porcine, chicken, bovine, canine, and feline coronaviruses, but will cover the research advances in human coronaviruses (HCoVs), in the discovery of host restriction factors for entry
Based on the crystal structure of SARS-CoV receptor-binding domain (RBD) complexed with hACE2 [83], a total of 14 amino acids in the RBD interact with angiotensinconverting enzyme 2 (ACE2)
The S2 domain contains several structurally conserved regions: fusion peptide (FP), two heptad repeats (HRs), TM domain, and cytoplasmic tail (Figure 2), all of which contribute to membrane fusion
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Cell entry is the first and essential step of virus infection (Figure 1) It is an ongoing process, conceptually, it can be divided into two steps: cell binding and membrane fusion. Many factors affect virus entry, tissue tropism, persistence, virulence, and host range These include the specific receptor usage, binding to attachment factors, susceptibility to protease cleavage, acid-induced conformational changes, and host restriction factors [4,5,6]. We primarily focus on the cell entry of coronaviruses infecting economically significant animals and pets, including porcine, chicken, bovine, canine, and feline coronaviruses, but will cover the research advances in human coronaviruses (HCoVs), in the discovery of host restriction factors for entry
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