A Central Science report from the CAS division of the American Chemical Society details developments and recommends directions against COVID-19 pandemic.
Investigators across the globe are racing to develop effective interventions against the COVID-19 pandemic. A new report from the Chemical Abstracts Services (CAS) division of the American Chemical Society details the array of potential treatments and diverse directions of research.
In their report, "Research and Development on Therapeutic Agents and Vaccines for COVID-19 and Related Human Corona" Cynthia Liu, PhD, manager of scientific information at CAS, and colleagues describe candidate products and promising research directions, and uncover biochemical patents that could yield therapeutic breakthroughs.
"Although more work remains to be done, the methodology and results presented in this special report may point to strategies that could help streamline the process of drug development for COVID-19 and provide intellectual groundwork for the ongoing efforts and future breakthroughs," Liu said, in a separately published commentary.
The quickest route to a therapeutic agent could be "repurposing" a currently available medication, according to the report authors.
"Given the lengthy process of new drug development, the current strategy of drug repurposing has become one of the chosen solutions for immediate treatment of SARS-CoV-2 infected individuals," Liu and colleagues indicate.
There is no information as of yet to guide prescribers on whether such medications would be useful or harmful to provide. However, the report identifies a dozen products which, it indicates, have been suggested by the scientific community to have therapeutic potential based on "genomic sequence information coupled with protein structure modeling".
Among the products is the anti-malarial chloroquine, which is in use against COVID-19 in China.
The possible mechanism of action of chloroquine on COVID-19, according to the CAS report, is the elevation of endosomal pH and interference with ACE2 glycosylation. Agents identified in the report as currently in trials for repurposing against COVID-19 include the anti-HIV agent lopinavir, an anti-Ebola and Marburg virus agent remdesivir, the anti-influenza agent Arbidol, and ribavirin, in use for hepatitis C, respiratory syncytial virus, and some viral hemorrhagic fevers.
The CAS report also identifies patents from its collection which relate to coronavirus key proteins. It notes that 3CLpro and RdRp proteins appear to be of greatest interest for potential interventions, and attribute this to earlier efforts to target these proteins on the SARS-CoV virus, which circulated in 2003.
Other patents of compounds that the report finds to have potential for repurposing against COVID-19 include a preparation of azetidine and cyclobutane deriviatives, acting as Janus kinase (JAK) inhibitors, a mechanism in treating rheumatoid arthritis; and a preparation of polycyclic pyridone derivatives, inhibiting the cap-dependent endonuclease (CEN) step of viral RNA transcription, targeted in developing influenza treatment.
The report identifies multiple approaches to vaccine development, including use of the attenuated virus and virus-like particles, as well as protein- DNA- and mRNA-based vaccines. Additional programs with biologics involve antibodies, cytokines and RNA therapies.
"The information provided in this report provides a strong intellectual groundwork for support of ongoing research and development for discovery and development of therapeutic agents and vaccines for treatment of COVID-19 and coronavirus-related diseases," Liu and colleagues declare.