Inhibitory effects of selected isoquinoline alkaloids against main protease (Mpro) of SARS-CoV-2, in silico study

Abstract

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global threat. Despite the production of various vaccines and different treatments, finding natural compounds to control COVID-19 is still a challenging task. Isoquinoline alkaloids are naturally occurring compounds known to have some potential antiviral activity. In this study, ten abundant isoquinoline alkaloids with antiviral activity were selected to analyze the preventive effect on COVID-19. A scrutinized evaluation based on Lipinski’s rule showed that one out of ten compounds was toxic. Based on molecular docking analysis using Autodock software one of the best molecules with maximum negative binding energy was selected for further analysis. The Gromacs simulation analysis revealed that Coptisine has more action against active site M pro of COVID-19. Overall, to make a rational design of various preventive analogues that inhibit the COVID-19, associated in vitro and in vivo analyses are needed to confirm this claim.

((E)‐N′(3,5‐di‐tert‐butil‐2‐hedroxybenzilidene)‐2‐hydroxybenzohydrazide (H3sahz)2 Copper (II) Complex: Synthesis, Crystal Structures, in silico Evaluations, and Enzymatic Inhibition

“…Molecular docking is an effective computer method in receptor/ligand interactions. This approach provides a comprehensive opinion of the enzyme/inhibitor binding details and can be supplementary in vitro data [36] . Molecular docking outcomes display the enzyme residues that are bound with inhibitors and offer the docking score conformation complex.…”

“…This approach provides a comprehensive opinion of the enzyme/inhibitor binding details and can be supplementary in vitro data. [36] Molecular docking outcomes display the enzyme residues that are bound with inhibitors and offer the docking score conformation complex. Synthetic complex and acarbose were docked into the αglucosidase enzyme.…”

Bioactivity and In Silico Studies of Isoquinoline and Related Alkaloids as Promising Antiviral Agents: An Insight

“…A recent in silico study, using Autodock (version 4.2) on selected isoquinoline alkaloids including cephaeline, coptisine, galanthamine, glaucine, drotaverine, chelidonine, hydrastine, boldine, fumaricin stated that coptisine had the best binding affinity (−9.15 kcal/mol) toward M pro . MD simulation study of coptisine depicted a stable complex of N3-M pro with a binding energy of −8.17 kcal/mol [54].…”

In Silico Evaluation of 1‐Aminoisoquinoline Derivatives against Dengue Virus: Greener Access via a Sonochemical Method

“…[7][8][9] For example, the antiviral activities of isoquinoline drugs against rhinoviruses were described [10] way back in 1970 whereas potential of selected isoquinoline alkaloids against main protease (M pro ) of SARS-CoV-2 was explored recently. [11] Sim-ilarly, the isoquonolines were also explored against the RNAcontaining flaviviruses including dengue viruses in 1992. [12a] On the other hand, berberine (B, Figure 1) an isoquinoline alkaloid has been shown to have virucidal activity against dengue virus in addition to zika as well as chikungunya virus.…”

“…The antiviral activities of isoquinolines are also not uncommon in the literature [7–9] . For example, the antiviral activities of isoquinoline drugs against rhinoviruses were described [10] way back in 1970 whereas potential of selected isoquinoline alkaloids against main protease (M pro ) of SARS‐CoV‐2 was explored recently [11] . Similarly, the isoquonolines were also explored against the RNA‐containing flaviviruses including dengue viruses in 1992 [12a] .…”