While vaccination has proven to be an effective strategy to prevent Covid-19, the need exists for inexpensive, room-temperature stable, and orally bioavailable therapeutics for COVID-19. Reasons for this need include the large percentage of individuals that have chosen to remain unvaccinated, the logistics and expense of distributing the vaccines worldwide, the reduction in efficacy that is seen for certain variants, and the expected need to continuously require booster shots due to waning immunity.
Anixa’s program in collaboration with European partner MolGenie, focuses on identifying novel, small molecule inhibitors of Mpro, the main protease of the virus. The current compounds that Anixa is synthesizing and evaluating have demonstrated their ability to inhibit the function of this protein, which the virus needs to replicate.
A key attribute of a successful therapeutic is the need to be effective against the prevailing variants that are circulating, especially if such emerging variants are more infectious. Since the authorized vaccines target a surface protein of the SARS-CoV-2, known as the spike protein, variants demonstrating variability in evading the vaccines are characterized by mutations in this protein. The prevailing variant of concern is known as the Delta variant.
In an attempt to evaluate whether the compounds Anixa is developing might be effective against the Delta variant, Anixa undertook an analysis of the corresponding Mpro enzyme mutations in the Delta variant. While mutations in the spike protein do not necessarily force a mutation in other functional proteins like Mpro, Anixa’s analysis and published work demonstrate that a key mutation in Mpro does exist for the Delta variant. Sequence analysis of several Delta variant samples demonstrate that the Mpro enzyme often has a mutation that replaces an asparagine (an amino acid) with leucine (another amino acid) at position 142, near the binding site. This change makes the binding pocket of Mpro more hydrophobic. By virtue of this change, the analysis indicates that Anixa’s novel compounds will be stronger inhibitors of the variant Mpro than the wild-type (original).
“This analysis and conclusion is a theoretical study, but we are pleased that this analysis indicates that our compounds should be effective against the Delta variant,” stated Dr. Amit Kumar, President and CEO of Anixa Biosciences. “While this program is relatively early-stage in development, we have already received inbound calls from pharmaceutical companies and funding agencies interested in collaborating at the right time,” continued Dr. Kumar.
Dr. Lutz Weber, President and CEO of MolGenie, stated, “We continue to synthesize several candidate compounds to identify the most potent drug candidate which we will take into pre-clinical drug development.”
See press release