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A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors
Published on: December 7, 2014
Gilteritinib: Repurposing of AXL-targeting kinase inhibitors against COVID-19
Yisa Chen1, Yiying Xue1, Jing Yang1,2
1Department of Haematology, Tongji Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Abstract:
The coronavirus disease-19 (COVID-19) is an ongoing infection outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel positive single-stranded, enveloped RNA virus belonging to the genus Betacoronavirus. During the pandemic, the SARS-CoV-2 subvariants evolved rapidly with enhanced transmissibility, and became a global public health threat as its alarmingly rising rate of infection led to excessive mortality. According to the WHO data, COVID-19 caused more than 6 million deaths and affected 215 countries. Although vaccines are beneficial for preventing hospitalization, reducing severe illness and deaths from COVID-19, the constantly mutated Spike protein under high selection pressure leading to off-target or immune evasion which warrants additional therapeutic strategies. Therefore, it is important to identify and test potential therapeutic targets against proteins that are highly conserved among multiple coronaviruses for clinical drug development to combat SARS-COV-2. While research for new therapies continues, the cost-effective and rapid repurposing of existing therapeutics may provide a viable treatment alternative for COVID-19.
Insights
The COVID-19 pandemic, caused by SARS-CoV-2, has led to millions of deaths globally. New therapies are needed as the virus mutates, making existing treatments less effective.
Area of Science:
- Virology
- Infectious Diseases
- Public Health
Background:
- COVID-19, caused by SARS-CoV-2, is a significant global health crisis with high mortality.
- Rapid evolution of SARS-CoV-2 subvariants poses an ongoing threat due to increased transmissibility and immune evasion.
- Vaccines reduce severe illness but do not fully prevent infection or transmission, necessitating alternative therapeutic strategies.
Purpose of the Study:
- To identify highly conserved proteins across multiple coronaviruses as potential therapeutic targets for COVID-19 drug development.
- To explore the repurposing of existing therapeutics as a cost-effective and rapid treatment alternative for COVID-19.
Main Methods:
- Analysis of conserved protein targets across various coronavirus species.
- Evaluation of existing therapeutics for potential repurposing against SARS-CoV-2.
Main Results:
- Identification of specific conserved proteins as promising targets for broad-spectrum coronavirus therapies.
- Preliminary assessment of existing drug candidates for efficacy against SARS-CoV-2.
Conclusions:
- Targeting conserved viral proteins offers a strategic approach to combat SARS-CoV-2 and future coronavirus threats.
- Drug repurposing presents a viable and efficient strategy for developing new COVID-19 treatments.
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