A review on recent theoretical approaches made in the discovery of potential Covid-19 therapeutics

SARS CoV-2 virus (COVID-19) emerged as a highly infectious human pathogen in late 2019. Started in China but rapidly started spreading all over the world and soon became a pandemic. More than seven million deaths have been reported so far that devasted millions of families worldwide. Several drugs, such as hydroxychloroquine, chloroquine, remdesivir, favipiravir and arbidol have undergone some clinical studies since early 2020, but their safety concerns remained a serious issue. However, within an year from late 2019, several successful vaccines were invented to prevent people from the infection. Almost at the same time, two drugs were discovered. These are PAXLOVID™ (nirmatrelvir, ritonavir) from Pfizer and molnupiravir from Merck which were soon approved by the US-FDA, for emergency use in the treatment of COVID-19. But several challenges were soon reported in treatments with these drugs, particularly for those who are immunocompromised or have vaccine immunity and suffering for a long time from the infection (known as long-COVID). Complex issues for treatments of long-COVID patients continue to remain unresolved. Thus, discovery of new drugs to assist treatment for emerging COVID-19 problems is urgently needed. But it is important to note that discovery of new COVID-19 therapeutics, particularly small molecules is not a simple task. However, there are several excellent reviews on attempts for COVID-19 drug discovery including a handful of articles on theoretical approaches towards the goal. This review summarizes the theoretical attempts for discovery of COVID-19 drugs, their challenges and future opportunities along with efforts from the author’s lab.