Precision therapeutic targets for COVID-19.

Area of Science:

• Virology and Drug Discovery
• Infectious Diseases
• Molecular Biology

Background:

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, leading to significant global mortality and morbidity.
• Current treatments for COVID-19 are largely supportive, with limited efficacy, and no specific antiviral drugs are available.
• Viral mutations pose a challenge to treatment efficacy, necessitating strategies that target less mutable viral components.

Purpose of the Study:

• To review the efficacy of preclinical and clinical drugs targeting key SARS-CoV-2 replication steps.
• To assess drugs targeting the spike protein, main protease (Mpro), and RNA-dependent RNA polymerase (RdRp).
• To propose a multi-drug strategy for effective inhibition of SARS-CoV-2.

Main Methods:

• Evaluation of preclinical and clinical drug efficacy.
• Focus on drugs targeting conserved domains within the spike protein, Mpro, and RdRp.
• Analysis of advantages and limitations of targeting evolutionarily stable viral proteins.

Main Results:

• Identified drugs targeting essential viral proteins involved in entry, proteolytic activation, and transcription.
• Highlighted the potential of targeting conserved protein domains to overcome viral mutation challenges.
• Assessed the benefits and drawbacks of various therapeutic approaches against SARS-CoV-2.

Conclusions:

• A multi-drug cocktail targeting the spike protein, Mpro, and RdRp offers a promising strategy against SARS-CoV-2.
• Targeting evolutionarily conserved viral domains is crucial for developing durable antiviral therapies.
• This approach holds the potential to effectively inhibit viral replication and limit the spread of COVID-19.