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Host Cell and SARS-CoV-2-Associated Molecular Structures and Factors as Potential Therapeutic Targets
Jitendra Kumar Chaudhary1, Rohitash Yadav2, Pankaj Kumar Chaudhary3
1Department of Zoology, Shivaji College, University of Delhi, New Delhi 110027, India.
Abstract:
Coronavirus disease 19 (COVID-19) is caused by an enveloped, positive-sense, single-stranded RNA virus, referred to as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which belongs to the realm Riboviria, order Nidovirales, family Coronaviridae, genus Betacoronavirus and the species Severe acute respiratory syndrome-related coronavirus. This viral disease is characterized by a myriad of varying symptoms, such as pyrexia, cough, hemoptysis, dyspnoea, diarrhea, muscle soreness, dysosmia, lymphopenia and dysgeusia amongst others. The virus mainly infects humans, various other mammals, avian species and some other companion livestock. SARS-CoV-2 cellular entry is primarily accomplished by molecular interaction between the virus's spike (S) protein and the host cell surface receptor, angiotensin-converting enzyme 2 (ACE2), although other host cell-associated receptors/factors, such as neuropilin 1 (NRP-1) and neuropilin 2 (NRP-2), C-type lectin receptors (CLRs), as well as proteases such as TMPRSS2 (transmembrane serine protease 2) and furin, might also play a crucial role in infection, tropism, pathogenesis and clinical outcome. Furthermore, several structural and non-structural proteins of the virus themselves are very critical in determining the clinical outcome following infection. Considering such critical role(s) of the abovementioned host cell receptors, associated proteases/factors and virus structural/non-structural proteins (NSPs), it may be quite prudent to therapeutically target them through a multipronged clinical regimen to combat the disease.
Insights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, with varied symptoms. Targeting viral proteins and host cell receptors offers a potential multipronged treatment strategy.
Area of Science:
- Virology
- Infectious Diseases
- Molecular Biology
Background:
- COVID-19 is caused by SARS-CoV-2, a positive-sense, single-stranded RNA virus.
- The virus infects humans and various animal species, presenting diverse symptoms like fever, cough, and respiratory distress.
- SARS-CoV-2 belongs to the Coronaviridae family, genus Betacoronavirus.
Purpose of the Study:
- To elucidate the molecular mechanisms of SARS-CoV-2 entry and pathogenesis.
- To identify key viral and host factors involved in COVID-19 infection.
- To propose therapeutic strategies targeting critical viral and host components.
Main Methods:
- Analysis of viral structure and host-cell interactions.
- Review of scientific literature on SARS-CoV-2 infection pathways.
- Identification of host cell receptors and viral proteins crucial for infection.
Main Results:
- SARS-CoV-2 entry relies on the spike (S) protein binding to host ACE2 receptor.
- Other factors like NRP-1, NRP-2, CLRs, TMPRSS2, and furin play roles in infection and disease progression.
- Viral structural and non-structural proteins significantly influence clinical outcomes.
Conclusions:
- Host cell receptors and viral proteins are critical for SARS-CoV-2 infection and pathogenesis.
- Targeting these components offers a promising avenue for developing effective COVID-19 treatments.
- A multipronged therapeutic approach is recommended to combat the disease effectively.
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