Molecular Mechanism for Coronavirus Infection

Dear Colleagues,

Over the last two decades, humans have witnessed and suffered three major coronavirus pandemics, severe acute respiratory syndrome coronavirus (SARS-CoV or SARS-CoV-1) in 2002, Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, and more recently, causative pathogen of Coronavirus disease 2019 (COVID-19), SARS-CoV-2 in 2019. To date, seven coronaviruses are known to infect humans, with the first being identified in the mid-1960s.

Coronaviruses are a large family of enveloped viruses with a positive-sense single-stranded RNA genome. Coronavirus is considered one of the largest RNA viruses with a genome size of about 30 kilobases(kb), which encodes 16 nonstructural proteins (NSPs), 4 structural proteins, and several accessory proteins as in the case of SARS-CoV-2. Coronaviruses, consisting of four genera, namely Alphacoronavirus, Betacoronavirus, Deltacoronavirus, and Gammacoronavirus, can infect a wide range of avian and mammalian hosts besides humans.

Coronavirus like SARS-CoV-2 can be highly contagious, and the symptom after infection varies. Clinically, patients of older age (>60 years) and/or with pre-existing severe diseases (i.e., hypertension, diabetes, cardiovascular disease, or blood cancers) have a greater risk of developing severe disease and even death. SARS-CoV-2 can be transmitted by close contact and exposure to aerosol droplets carrying infectious virions. Starting from the infection of the nasal respiratory epithelial cells, the virus can further replicate in the airways and enter alveolar epithelial cells in the lungs, where it may trigger a robust immune response and even a cytokine storm.

The initial steps of coronavirus infection involve the specific binding of the coronavirus spike (S) protein to the cellular entry receptors. In the case of Human coronavirus NL63, SARS-CoV, and SARS-CoV-2, angiotensin-converting enzyme 2(ACE2) is identified as such a functional receptor. The trimerized S glycoproteins of coronavirus are shaped like a crown with subunits 1 (S1) and subunits 2 (S2) which engage receptor binding and membrane fusion, respectively. S1 contains the N-terminal domain (NTD) and receptor-binding domain (RBD). The RBD of S glycoprotein is not only one of the mutational hot spots of SARS-CoV-2 but also the most targeted region by neutralizing antibodies. Besides viral factors, host factors like proteases of furin, transmembrane serine protease 2 (TMPRSS2), and cathepsins are also involved in the pathogenesis of coronavirus infection.

SARS-CoV-2 has accumulated many mutations related to fitness advantages and immunological resistance with the persistence of the COVID-19 pandemic, resulting in numerous mutant strains (variants) reported over time. Of them, the variants of concern (VOCs; like Alpha, Beta, Gamma, Delta, and Omicron) attract wide attention as these variants have altered phenotypic characteristics and pose an imminent threat as they either exhibit higher transmissibility, have a detrimental change in COVID-19 epidemiology, increase in virulence, change in clinical disease presentation, or a decrease in the effectiveness of public health and social measures or available diagnostics, vaccines, therapeutics.

As we are going to enter year 4 of the coronavirus pandemic, much progress has been made in developing prophylaxis and therapeutic agents against coronavirus infection. However, there are still many actual problems in the field of molecular mechanisms for coronavirus infection. Of them, the underlying molecular mechanism responsible for the high level of viral transmissibility and broad tissue tropism or interspecies transmission remains largely unexplored; the characterization of the coronavirus infection process, as well as viral and host factors that are involved in the pathogenesis of viral infection; the development of novel or repurposed prophylaxis and therapeutic agents targeting host-pathogen interaction; the molecular mechanism underlying the waning effectiveness of COVID vaccines or drugs and possible viral breakthrough infections and immune evasion, etc., warrant further investigation.

For this Special Issue, we are seeking original research or review articles that will improve our knowledge of these topics mentioned above.

Dr. Qibin Geng
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

• COVID-19
• coronavirus infection
• SARS-CoV-2
• molecular mechanism
• molecular epidemiology
• vaccines or drugs
• pathogenicity or pathology
• animal models or studies
• mutants or variants
• interspecies transmission