A representative of novel MPro inhibitor series, MPI8, dually inhibits MPro and cathepsin L, a key viral entry enzyme, with high potency and selectivity.
Other analogs of the series have been evaluated by Sorrento to develop an oral antiviral drug for treatment of patients infected with existing and emerging SARS-CoV-2 variants of concern, including Omicron.
A promising candidate of the series with unique features distinguished from SARS-CoV-2 MPro inhibitors published by others has been systematically evaluated and advanced to late stage of pre-clinical phase.
SAN DIEGO, Dec. 05, 2021 (GLOBE NEWSWIRE) -- Sorrento Therapeutics, Inc. (Nasdaq: SRNE, "Sorrento") today announced the peer-reviewed publication of a series of novel SARS-CoV-2 MPro inhibitors with potent activities for both MPro and cathepsin L, a key host enzyme for SARS-CoV-2 entry into host cells, authored by Dr. Wenshe Ray Liu, professor at Texas A&M University.
The full manuscript is available
SARS-CoV-2 main protease (MPro) is a key enzyme for the viral life cycle including virus entry, replication and packaging. MPro is highly conserved in all discovered SARS CoV-2 variants and is identified as a critical target for developing broad-spectrum antiviral drugs. In addition, experimental evidence has shown that certain host proteases prime the SARS-CoV-2 spike protein for viral packaging, interactions with ACE2, and viral entry into the host. These include two serine proteases, furin and transmembrane protease serine 2 (TMPRSS2) and a cysteine protease cathepsin L. Small molecule medications that inhibit furin, TMPRSS2 and cathepsin L have shown efficacy in inhibiting SARS-CoV-2 replication. In the publication, a representative analog of the series, MPI8, demonstrated dual inhibition of MPro and cathepsin L with high potency and selectivity (IC50 values for MPro and cathepsin L are 105 nM and 1.2 nM, respectively). Sorrento has collaborated with Professor Liu's lab at Texas A&M University to evaluate analogs in the series to develop an oral anti-COVID drug. A promising analog with features distinguished from current reported SARS-CoV-2 MPro inhibitors has been systematically evaluated and advanced to a late stage of pre-clinical phase. "We are pleased to work with Prof. Liu's group at Texas A&M University to develop a more effective oral MPro inhibitor to meet the urgent need for treatment of COVID-19 patients infected with existing and emerging variants. The oral MPro inhibitor together with Sorrento's other ongoing therapeutic intervention approaches reflect our efforts to create a 'mutation-agnostic' global anti-COVID strategy to combat COVID-19 variants of concern, including the emerging Omicron variant," stated Dr. Henry Ji, Chairman and CEO of Sorrento.
"As a selective inhibitor to both SARS-CoV-2 MPro and cathepsin L that is key to SARS-CoV-2 entry into the human host cell, MPI8 exerts improved potency to inhibit SARS-CoV-2. So far it is potentially one of the most potent antivirals that have been developed to treat COVID-19," stated Dr. Wenshe Ray Liu, Gradipore Chair in the Department of Chemistry at Texas A&M University.
About Sorrento Therapeutics, Inc.
Sorrento is a clinical and commercial stage biopharmaceutical company developing new therapies to treat cancer, pain (non-opioid treatments), autoimmune disease and COVID-19. Sorrento's multimodal, multipronged approach to fighting cancer is made possible by its extensive immuno-oncology platforms, including key assets such as fully human antibodies ("G-MAB™ library"), immuno-cellular therapies ("DAR-T™"), antibody-drug conjugates ("ADCs"), and oncolytic virus ("Seprehvec™"). Sorrento is also developing potential antiviral therapies and vaccines against coronaviruses, including Abivertinib, COVIGUARD™, COVI-AMG™, COVISHIELD™, COVI-MSC™ and COVIDROPS™; and diagnostic test solutions, including COVITRACK™, COVISTIX™ and COVITRACE™.
Sorrento's commitment to life-enhancing therapies for...
(All Rights Reserved)