New Pfizer drug and ivermectin

New Pfizer antiviral and ivermectin, a pharmacodynamic analysis

New Pfizer antiviral, PF-07321332, C₂₃H₃₂F₃N₅O₄

PF-07321332 is designed to block the activity of the SARS-CoV-2-3CL protease,

https://www.pfizer.com/news/press-release/press-release-detail/pfizers-novel-covid-19-oral-antiviral-treatment-candidate

So, what is a protease?

So what is a protease inhibitor?

And, what is 3CL?

Chymotrypsin-like protease (3CL main protease, or 3CL Mpro)

Identification of SARS-CoV‑2 3CL Protease Inhibitors by a Quantitative High-Throughput Screening (3rd September 2020)

https://pubs.acs.org/doi/abs/10.1021/acsptsci.0c00108#

The activity of the anti-SARS-CoV-2 viral infection was confirmed in 7 of 23 compounds

Microscopic interactions between ivermectin and key human and viral proteins involved in SARS-CoV-2 infection

https://pubs.rsc.org/en/content/articlehtml/2021/cp/d1cp02967c

the strength and persistency of the interaction between IVE and the binding site of 3CLpro indicate that a partial inhibition of the catalytic activity could have place as the drug interacts with the main subdomains that define the enzyme binding pocket:

Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents

https://www.nature.com/articles/s42003-020-01577-x

as shown in Fig. 4, out of 13 OTDs only ivermectin completely blocked ( more than 80%) the 3CLpro activity at 50 µM concentration.

Development, validation, and approval of COVID-19 specific drugs takes years. Therefore, the idea of drug repositioning, also known as repurposing, is an important strategy to control the sudden outbreak of life-threatening infectious agents that spread rapidly.

Ilimaquinone (marine sponge metabolite) as a novel inhibitor of SARS-CoV-2 key target proteins in comparison with suggested COVID-19 drugs: designing, docking and molecular dynamics simulation study

https://pubs.rsc.org/en/content/articlehtml/2020/ra/d0ra06379g

From the docking analysis, ivermectin showed the highest docking score with an average energy of −8.5 kcal mol−1 among all the compounds. Remdesivir showed the lowest binding energy and highest docking score of −9.9 kcal mol−1

https://bnf.nice.org.uk/medicinal-forms/remdesivir.html

Ritonavir, C37H48N6O5S2

Ivermectin, C48H74O14

Exploring the binding efficacy of ivermectin against the key proteins of SARS-CoV-2 pathogenesis: an in silico approach

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996102/

We have documented an intense binding of both ivermectin B1a and B1b isomer to the main protease with subsequent energy (ETot-) values of -384.56 and -408.6.