COVID-19 and the promise of small molecule therapeutics: Are there lessons to be learnt?

Abstract

The coronavirus disease 2019 (COVID-19) pandemic had grounded the world to a standstill. As the disease continues to rage two years on, it is apparent that effective therapeutics are critical for a successful endemic living with COVID-19. A dearth in suitable antivirals has prompted researchers and healthcare professionals to investigate existing and developmental drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although some of these drugs initially appeared to be promising for the treatment of COVID-19, they were ultimately found to be ineffective. In this review, we provide a retrospective analysis on the merits and limitations of some of these drugs that were tested against SARS-CoV-2 as well as those used for adjuvant therapy. While many of these drugs are no longer part of our arsenal for the treatment of COVID-19, important lessons can be learnt. The recent inclusion of molnupiravir and Paxlovid™ as treatment options for COVID-19 represent our best hope to date for endemic living with COVID-19. Our viewpoints on these two drugs and their prospects as current and future antiviral agents will also be provided.

Keywords: Antivirals; Baricitinib (PubChem CID: 44205240); COVID-19; Chloroquine (PubChem CID: 2719); Dexamethasone (PubChem CID: 5743); Drug discovery; Hydroxychloroquine (PubChem CID: 3652); Ivermectin (PubChem CID: 6321424); Lopinavir (PubChem CID: 92727); Molnupiravir (Pubchem CID: 145996610); Nirmatrelvir (PubChem CID: 155903259); Remdesivir (PubChem CID: 121304016); Ritonavir (PubChem CID: 392622); Small molecule therapeutics.