In SilicoDe Novo Curcuminoid Derivatives From the Compound Library of Natural Products Research Laboratories Inhibit COVID-19 3CLproActivity

Abstract

The coronavirus disease 2019 (COVID‐19) outbreak caused by the 2019 novel coronavirus (2019-nCOV) is becoming increasingly serious. In March 2019, the Food and Drug Administration (FDA) designated remdesivir for compassionate use to treat COVID-19. Thus, the development of novel antiviral agents, antibodies, and vaccines against COVID-19 is an urgent research subject. Many laboratories and research organizations are actively investing in the development of new compounds for COVID-19. Through in silico high-throughput virtual screening, we have recently identified compounds from the compound library of Natural Products Research Laboratories (NPRL) that can bind to COVID-19 3Lpropolyprotein and block COVID-19 3Lproactivity through in silico high-throughput virtual screening. Curcuminoid derivatives (including NPRL334, NPRL339, NPRL342, NPRL346, NPRL407, NPRL415, NPRL420, NPRL472, and NPRL473) display strong binding affinity to COVID-19 3Lpropolyprotein. The binding site of curcuminoid derivatives to COVID-19 3Lpropolyprotein is the same as that of the FDA-approved human immunodeficiency virus protease inhibitor (lopinavir) to COVID-19 3Lpropolyprotein. The binding affinity of curcuminoid derivatives to COVID-19 3Lprois stronger than that of lopinavir and curcumin. Among curcuminoid derivatives, NPRL-334 revealed the strongest binding affinity to COVID-19 3Lpropolyprotein and is speculated to have an anti-COVID-19 effect. In vitro and in vivo ongoing experiments are currently underway to confirm the present findings. This study sheds light on the drug design for COVID-19 3Lpropolyprotein. Basing on lead compound development, we provide new insights on inhibiting COVID-19 attachment to cells, reducing COVID-19 infection rate and drug side effects, and increasing therapeutic success rate.