Abstract
A global pandemic has emerged following the appearance of the new severe acute respiratory virus whose official name is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), strongly affecting the health sector as well as the world economy. Indeed, following the emergence of this new virus, despite the existence of a few approved and known effective vaccines at the time of writing this original study, a sense of urgency has emerged worldwide to discover new technical tools and new drugs as soon as possible. In this context, many studies and researches are currently underway to develop new tools and therapies against SARS CoV-2 and other viruses, using different approaches. The 3-chymotrypsin (3CL) protease, which is directly involved in the cotranslational and posttranslational modifications of viral polyproteins essential for the existence and replication of the virus in the host, is one of the coronavirus target proteins that has been the subject of these extensive studies. Currently, the majority of these studies are aimed at repurposing already known and clinically approved drugs against this new virus, but this approach is not really successful. Recently, different studies have successfully demonstrated the effectiveness of artificial intelligence-based techniques to understand existing chemical spaces and generate new small molecules that are both effective and efficient. In this framework and for our study, we combined a generative recurrent neural network model with transfer learning methods and active learning-based algorithms to design novel small molecules capable of effectively inhibiting the 3CL protease in human cells. We then analyze these small molecules to find the correct binding site that matches the structure of the 3CL protease of our target virus as well as other analyses performed in this study. Based on these screening results, some molecules have achieved a good binding score close to -18 kcal/mol, which we can consider as good potential candidates for further synthesis and testing against SARS-CoV-2.
Highlights
The presence of coronaviruses constitutes a serious threat for the human population
A new type of virus known as the new SARS-CoV-2 or COVID-19 coronavirus was discovered in Wuhan, China (CO-Coronavirus, VI-Coronavirus, D-December, 19-2019) [1]
We wanted to generate smaller, targeted collections enriched with molecules that are potentially active for a specific target in particular, in our case SARS-CoV-2
Summary
The presence of coronaviruses constitutes a serious threat for the human population. these viruses belong to a large family that causes a variety of diseases ranging from the common cold to more serious diseases that attack the human respiratory system. A new type of virus known as the new SARS-CoV-2 or COVID-19 coronavirus was discovered in Wuhan, China (CO-Coronavirus, VI-Coronavirus, D-December, 19-2019) [1]. Despite the existence of new vaccines that have been approved and are in use, the current lack of effective drugs against these coronaviruses has slowed the countless efforts to stop the spread of SARS-CoV-2 worldwide. Despite this delay in finding appropriate therapies, the threats posed by coronaviruses should not be underestimated and it is essential to advance our research to understand how coronaviruses replicate while interacting with their hosts so BioMed Research International that appropriate and effective treatments can be developed as soon as possible. These successive outbreaks have clearly highlighted the long-term threat of interspecies transmission events leading to human epidemics and the possible reemergence of similar viral infections, which must be seriously considered [7]
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