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Updated: Dec 3, 2025
Arbovirus Infections As Screening Tools for the Identification of Viral Immunomodulators and Host Antiviral Factors
Published on: September 13, 2018
Targeting Crucial Host Factors of SARS-CoV-2
Anil Mathew Tharappel1, Subodh Kumar Samrat1, Zhong Li1
1Wadsworth Center, New York State Department of Health, 120 New Scotland Avenue, Albany, New York 12208, United States.
Insights
Targeting host factors offers broader therapeutic strategies against SARS-CoV-2 than targeting viral proteins, potentially reducing drug resistance for COVID-19 treatment.
Area of Science:
- Virology
- Infectious Diseases
- Drug Discovery
Background:
- Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has a high transmission rate, necessitating rapid therapeutic development.
- Viral protein targets for COVID-19 therapies face challenges due to frequent mutations and limited viral proteins, potentially leading to drug resistance.
- Host factor targeting presents a promising alternative for broader and more durable therapeutic interventions against SARS-CoV-2 and related viruses.
Purpose of the Study:
- To review the role of primary host factors in SARS-CoV-2 infection.
- To discuss the pharmacological interventions targeting these host factors.
- To highlight the advantages of host factor targeting over viral protein targeting for COVID-19 therapy.
Main Methods:
- Literature review of host factors involved in SARS-CoV-2 life cycle.
- Analysis of viral entry and replication mechanisms.
- Examination of pharmacological strategies targeting host factors like ACE2 and proteases.
Main Results:
- Host factors, including ACE2 and proteases, are crucial for SARS-CoV-2 entry and replication.
- Targeting host factors may offer broader therapeutic efficacy and reduce the risk of drug resistance compared to targeting viral proteins.
- Specific host factors like ACE2, S protein priming proteases, kinases, and inflammatory cells are key targets for intervention.
Conclusions:
- Host factor-based therapies hold significant potential for treating COVID-19 and related viral infections.
- Targeting cellular mechanisms provides a more robust strategy against viral evolution and resistance.
- Further research into pharmacological interventions for host factors is warranted to combat the COVID-19 pandemic.
Abstract:
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide since its first incidence in Wuhan, China, in December 2019. Although the case fatality rate of COVID-19 appears to be lower than that of SARS and Middle East respiratory syndrome (MERS), the higher transmissibility of SARS-CoV-2 has caused the total fatality to surpass other viral diseases, reaching more than 1 million globally as of October 6, 2020. The rate at which the disease is spreading calls for a therapy that is useful for treating a large population. Multiple intersecting viral and host factor targets involved in the life cycle of the virus are being explored. Because of the frequent mutations, many coronaviruses gain zoonotic potential, which is dependent on the presence of cell receptors and proteases, and therefore the targeting of the viral proteins has some drawbacks, as strain-specific drug resistance can occur. Moreover, the limited number of proteins in a virus makes the number of available targets small. Although SARS-CoV and SARS-CoV-2 share common mechanisms of entry and replication, there are substantial differences in viral proteins such as the spike (S) protein. In contrast, targeting cellular factors may result in a broader range of therapies, reducing the chances of developing drug resistance. In this Review, we discuss the role of primary host factors such as the cell receptor angiotensin-converting enzyme 2 (ACE2), cellular proteases of S protein priming, post-translational modifiers, kinases, inflammatory cells, and their pharmacological intervention in the infection of SARS-CoV-2 and related viruses.
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