With the world still only a few months into the COVID-19 pandemic, researchers are working furiously to keep up with all the newly discovered information about the virus. To help share the information and promote greater understanding, CAS has released Potential Therapeutic Agents and Associated Bioassay Data for COVID-19 and Related Human Coronavirus Infections, a report designed to put comprehensive, up-to-date information in the hands of researchers around the world.
CAS is a section of the American Chemical Society that focuses on sharing scientific information solutions. Outsourcing-Pharma (OSP) recently discussed the report with CAS information scientist and study author Angela Zhou (AZ), and how the information might help make a difference in the development of solutions to treat the deadly virus.
OSP: Could you please tell us how this report came to be?
AZ: In March, as information about the pandemic began to spread in the scientific community, a group of CAS scientists came together who were passionate about using our unique assets and capabilities in organizing and connecting global scientific information to help in the research efforts related to COVID-19. Additional scientists with expertise in therapeutics, virology, protein biochemistry and data analysis who speak dozens of languages were recruited to help develop this report; they worked tirelessly to rapidly gather and analyze all relevant published scientific information and wrote one of the first review articles on potential drugs for COVID-19 based on previous research on related viruses SARS and MERS. This initial work was published in ACS Central Science in March.
The authors, and other colleagues, then turned our attention to what additional information would be most helpful to researchers. As work ramped up worldwide and a large volume of additional publications specific to SARS-CoV-2 with laboratory research data emerged, there was a clear need to augment the initial review with new information.
It was also evident that there was high interest in the growing volume of experimental bioassay data that helps researchers evaluate and prioritize the large volume of potential drug candidates. To address these needs, we decided to write this second report summarizing the most current research on SARS-CoV-2 therapeutics, but also providing a consolidated view of existing substances that have been tested to be effective with related coronaviruses SARS-CoV and MERS-CoV and the associated bioactivity data. This report was recently published in ACS Pharmacology and Translational Medicine.
OSP: What were the goals of the CAS team in creating and distributing this report?
AZ: It was really about doing everything we could, using the unique resources and expertise of CAS, to expedite development of COVID-19 therapeutics. In light of the enormous amount of published information and rapidly evolving knowledge about COVID-19, we wanted to systematically assemble and curate this large amount of data into one comprehensive resource.
We are hoping that this report serves as a resource to scientists in pharmaceutical companies and research organizations who are actively involved in COVID-19 drug discovery. It will save them time and help them have a complete view of the work to date and relevant data, so that they can build upon it efficiently.
This report demonstrates CAS’s unique capability in assembling and analyzing large amounts of diverse chemical and biological substance information based on specific target proteins from global published research. Given the volume of research and related data, and the fact that it is published in many global languages, this is a task that it would be nearly impossible for any single research group or organization to tackle individually, which is why CAS was created in the first place more than 110 years ago.
By collecting, analyzing and connecting global scientific data, we help scientists around the world work more efficiently and provide insights that drive new discoveries.
OSP: Which groups of people in the field is this document targeted toward?
AZ: Primarily scientists, medicinal chemists and those in the drug research and discovery field; organizations like pharmaceutical companies, research institutes and universities. Though we have also published a number of large open access data sets of potential antiviral drug candidates, proteins, and structure activity relationships that can support the work of data scientists and those take in silico approaches to tackling COVID-19 as well.
OSP: Could you please tell us some of the key information included in the resource?
AZ: This most recent report discusses the various viral and human proteins as key targets for potential COVID-19 drugs as well as relevant potential drug candidates known to inhibit these drug targets, including those already being tested with SARS-CoV-2, as well as those previously validated in SARS-CoV or MERS-CoV. The report also includes a number of valuable datasets extract from the CAS content collection, which is the world’s largest repository of human-curated scientific information:
- A comprehensive list of viral and human proteins that may serve as potential drug targets in COVID-19
- Several sets of chemical or protein substances categorized according to the proteins they could target.
- Detailed data, found in tables and supporting information, such as substance names, CAS REGISTRY numbers, chemical structures and bioassay data.
OSP: Would you say there are any surprises or especially interesting findings therein?
AZ: Though not necessarily surprising, it has been interesting to see that some of the substances included in this report that were identified based on previously published bioassay data with SARS-CoV and MERS-CoV have, after its publication, been confirmed to show efficacy against SARS-CoV-2. One example is GRL-0617, a PLpro inhibitor. This is further evidence that those substances from SARS-CoV and MERS-CoV research, which we have cataloged in the publication, should be high priority candidates for further evaluation for SARS-CoV-2.
The absence of published data in some areas has been surprising. For example, not a lot of chemical substances have been tested as inhibitors of coronavirus RdRp, an enzyme needed for the assembling of viral genetic material (RNA). However, RdRp inhibitors of hepatitis C virus (HCV), another RNA virus, have been widely researched; these HCV RdRp inhibitors could be another good starting point for those seeking coronavirus RdRp inhibitors or a broad spectrum RdRp inhibitor that could work in multiple types of RNA viruses.
It has also been amazing to see how much our understanding of this new virus has grown and evolved in just a few months. For example, while the initial focus was on the ACE2 receptor as being the primary human protein involved in viral entrance, additional research has identified other proteins such as furin and TMPRSS2 that have also been found to play important roles; this is very valuable because each new protein target provides new and different therapeutic opportunities and there are already extensive data on chemical inhibitors of furin and TMPRSS2 that may be relevant to treating COVID-19.
OSP: How do you think or hope this resource will be put to use?
AZ: We hope that the bioassay data with detailed structure-activity relationship information extracted from published studies will be valuable to the ongoing drug repurposing efforts and the discovery of new therapeutics with the potential for treating COVID-19. If it saves scientists a few months, days or weeks in getting a new drug in the hands of patients who need it, then we have achieved our goal.
OSP: Is there anything else you’d like to add, about the report or COVID-19 research in general?
AZ: Just want to continue to get the word out that, aligned with of our mission as a division of the American Chemical Society, CAS is committed to doing everything in our power to enable and accelerate COVID-19 research. All the datasets, resources, and publications we have produced can be accessed directly at www.cas.org/covid19 and through our Custom Services function, we have also offered to consult with research teams working directly on COVID-19 therapeutics at no cost to the extent our capacity will allow to address needs for customer queries, data curation, translation, or specialized scientific expertise.