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A Brief Review of SARS-CoV2 Therapeutics
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This week we have a short post discussing a recent review article discussing available Covid therapeutics along with other associated news from around the web.
A Review of Covid Therapeutics
Here is a nice review of available SARS-Cov-2 therapeutics that recently came out. There have been a very broad range of therapeutic strategies developed for Covid treatment, with over 700 agents reported to have anti SARS-Cov-2 activity in preclinical/clinical settings. Of these, about 20 have been approved for human treatment (table). Of these, 11 are monoclonal antibodies and the rest small molecules.
Broadly, the therapeutic strategy for an antiviral is to target either a viral protein or a host protein in the human cell. As the figure below shows, there are a number of different proteins on either the human or viral that can be potentially targeted. Viral targets can have higher selectivity and fewer side effects, but can be rendered ineffective by mutations in the virus. Human targets have greater potential for side effects, but have lower risk of drug resistance developing.
A broad range of monoclonal antibodies have been developed for Covid treatment. These antibodies often target the Covid spike protein on the exterior of the viral capsid as shown in the figure below. Combinations of multiple classes of antibodies can be used to handle multiple SARS-Cov-2 variants.
A number of small molecule therapeutics (such as remdesivir, and molnupravir) target various viral and human proteins. Another common therapeutic strategy is to target the immune response. This doesn’t directly treat the disease, but can control overactive immune responses. Corticosteroids are a common treatment in this vein. Janus Kinase (JAK) inhibitors are another class of such therapeutics; JAK inhibitors such as baricitinib originally approved for rheumatoid arthritis have been repurposed for Covid treatment. Anticoagulants have also been used to lower the risk of blood clots in patients with severe cases of Covid.
A major challenge for SARS-Cov-2 therapeutic development in general is the lack of high fidelity assays. The Vero E6 African Monkey cell line is commonly used in papers, but non-human cell lines are very imperfect models of the disease. Broader usage of improved human cell line assays, perhaps based on differentiated primary airway epithelial cells, or human Calu-3 lung cells could help accelerate therapeutic design. The review article as a whole is worth a read for anyone interested in learning more about the current status of Covid therapeutics.
Interesting Links from Around the Web
https://spectrum.ieee.org/ai-software: AI powered development tools could worsen security vulnerabilities.
https://www.extremetech.com/cars/toyota-reveals-plans-for-a-900-mile-solid-state-ev-battery: Toyota aims for a 900 mile EV battery by 2028.
https://thehighergeometer.wordpress.com/2023/04/19/joshis-quest/#comment-19198, and https://www.math.arizona.edu/~kirti/Response-to-grouchy-expert.pdf: Some back and forth on Kirti Joshi’s work on the ABC conjecture
https://www.nature.com/articles/d41586-023-01965-3, https://www.nature.com/articles/s41586-023-06096-3: IBM scales to more sophisticated quantum calculations on its quantum computer.
https://www.science.org/content/article/major-us-geological-survey-aims-uncover-minerals-critical-batteries-microchips: The USGS is attempting to find more mineral deposits within the US
https://www.jmlr.org/papers/volume23/20-1433/20-1433.pdf: Dropout networks are universal approximators
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Author: Bharath Ramsundar, Ph.D.
Editor: Sandya Subramanian, Ph.D.