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Published on: December 23, 2020
Molecular Targets in the Chemotherapy of Coronavirus Infection
O P Zhirnov1,2
1The Russian-German Academy of Medical and Biotechnological Sciences, Moscow, 121205, Skolkovo, Russia. zhirnov@inbox.ru.
Abstract:
In the pathogenesis of the infectious process in the respiratory tract by SARS, MERS, and COVID-19 coronaviruses, two stages can be distinguished: early (etiotropic) and late (pathogenetic) ones. In the first stage, when the virus multiplication and accumulation are prevalent under insufficient host immune response, the use of chemotherapeutic agents blocking the reproduction of the virus is reasonable to suppress the development of the disease. This article considers six major chemotherapeutic classes aimed at certain viral targets: inhibitors of viral RNA polymerase, inhibitors of viral protease Mpro, inhibitors of proteolytic activation of viral protein S allowing virus entry into the target cell, inhibitors of virus uncoating in cellular endosomes, compounds of exogenous interferons, and compounds of natural and recombinant virus-neutralizing antibodies. In the second stage, when the multiplication of the virus decreases and threatening pathological processes of excessive inflammation, acute respiratory distress syndrome, pulmonary edema, hypoxia, and secondary bacterial pneumonia and sepsis events develop, a pathogenetic therapeutic approach including extracorporeal blood oxygenation, detoxification, and anti-inflammatory and anti-bacterial therapy seems to be the most effective way for the patient's recovery.
Insights
This study explores two stages of coronavirus infections, focusing on early antiviral therapies and later pathogenetic treatments for severe respiratory illness. Effective management requires targeting viral replication initially, then addressing inflammation and secondary complications.
Area of Science:
- Virology
- Infectious Diseases
- Respiratory Medicine
Background:
- Coronaviruses like SARS, MERS, and COVID-19 cause respiratory tract infections with distinct pathogenic stages.
- Understanding these stages is crucial for developing effective therapeutic strategies.
Purpose of the Study:
- To outline distinct therapeutic approaches for the early and late stages of coronavirus infections.
- To review key chemotherapeutic agents and pathogenetic treatments relevant to these stages.
Main Methods:
- Review of six major chemotherapeutic classes targeting viral replication mechanisms.
- Discussion of pathogenetic therapies for managing severe complications in later disease stages.
Main Results:
- Early-stage treatment focuses on inhibiting viral RNA polymerase, protease Mpro, viral entry, uncoating, and utilizing interferons and antibodies.
- Late-stage treatment emphasizes managing excessive inflammation, acute respiratory distress syndrome, and secondary infections.
Conclusions:
- A dual therapeutic strategy is essential: etiotropic therapy for viral suppression in early stages and pathogenetic therapy for managing severe sequelae in later stages.
- Integrated treatment including extracorporeal oxygenation, detoxification, and anti-infective measures is vital for patient recovery.
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