In Silico Study of the Active Compounds of Lindera aggregata (Sims) Kosterm as Anti-coronavirus

Abstract

Background: Covid-19, caused by a new type of coronavirus named SARS-CoV-2, has become a pandemic. Together with SARS-CoV and MERS-CoV, Covid-19 is a large global outbreak of coronavirus infection; however, its rate of spread is much higher. Since the vaccines and anti-SARS-CoV-2 have not been found, a faster control mechanism is needed. Traditional herbs have shown the potential for this purpose, as has been demonstrated by the Chinese Government with a high success rate. One of the herbs used was Lindera aggregata, which is part of the collection in Purwodadi Botanic Garden. Objectives: Through in silico study, this research aims to reveal the secondary metabolites contained in L. aggregata that have the potential to serve as anti-SARS-CoV-2 medication as well as showcase their inhibitory mechanisms. Methods: The research was conducted through molecular docking analysis of terpenoids and alkaloids contained in the root of L. aggregata, with target proteins 3CLpro, PLpro, Spike, and ACE 2 playing a role in SARS-CoV-2 infection. Result: All analyzed compounds tended to interact with all four target proteins with different binding affinity values, but the interaction seemed stronger with 3CLpro and Spike. Terpenoids, linderane and linderalactone, had the strongest interaction tendency with 3CLpro, PLpro, and Spike; the compound norboldine, an alkaloid, had the strongest interaction with ACE 2, with a binding affinity value of -8.2 kcal/mol. Conclusion: Terpenoids and alkaloids contained in the root of L. aggregata, which caused inhibition of adsorption and replication of SARS-CoV-2, could serve as anti-SARS-CoV-2.

The naturally‐derived alkaloids as a potential treatment for COVID‐19: A scoping review

“…Overall, 11 studies (25.58%) approached the spike glycoprotein as target protein, being the alkaloids analyzed the following: crambescidin 826, cryptospirolepine, deoxynortryptoquivaline, ergotamine, hyoscyamine, nicotine docking on soluble angiotensin‐converting enzyme II receptor in complex with spike (S) protein of Indian SARS‐CoV‐2 (sACE2‐INS1), nigellidine, norbolidine, pallidine, piperine and quinadoline B (Borquaye et al, 2020 ; El‐Demerdash et al, 2021 ; Firdiana et al, 2021 ; Gyebi et al, 2020 ; Ismail et al, 2021 ; Selvaa Kumar, Kumar, & Wei, 2020 ; Maiti, Banerjee, & Kanwar, 2021 ; Maiti, Banerjee, Nazmeen, Kanwar, & Das, 2020 ; Mao, Bie, Xu, Wang, & Gao, 2021 ; Ogunyemi et al, 2020 ; Skariyachan, Gopal, Muddebihalkar, & Uttarkar, 2021 ).…”

“…The alkaloids nicotine, nigellidine, norboldine, piperine, quinadoline A and trytoquivaline showed binding capacity to the angiotensin‐converting enzyme II (ACE2) (Firdiana et al, 2021 ; Ismail et al, 2021 ; Maiti et al, 2021 ; Maurya, Kumar, Prasad, Bhatt, & Saxena, 2020 ; Selvaa Kumar, Kumar, & Wei, 2020 ).…”

“…Alkaloids norquinadoline A, scedapin C, schizanthin Z, ergotamine, and norboldine demonstrated significant bindings with the PLpro of SARS‐CoV‐2 (Alfaro, Alfaro, & Angel, 2020 ; Firdiana et al, 2021 ; Jade et al, 2021 ; Quimque et al, 2020 ). The alkaloid nigellidine showed possible anti‐SARS‐CoV‐2 activity through a good binding energy (−6.60 kcal/mol) with nonstructural protein 2 (NSP2), as well as quinine presented similar energy of −6.14 kcal/mol for nonstructural protein 12 (NSP12) target (Maiti et al, 2020 ; Sumitha, Devi, Hari, & Dhanasekaran, 2020 ).…”

“…Noscapine, leuconicine F, nigellidine, epiisopiloturine, camptothecin, anisotine, norboldine were also analyzed through molecular docking for Mpro target (de Sá et al, 2021 ; Devasia et al, 2021 ; Firdiana et al, 2021 ; Ghosh, Chakraborty, Biswas, & Chowdhuri, 2020 ; Jade et al, 2021 ; D. Kumar, Kumari et al, 2020 ; N. Kumar, Sood, van der Spek, Sharma, & Chandra, 2020 ; Maiti et al, 2020 ).…”

Jeopardy of COVID-19: Rechecking the Perks of Phytotherapeutic Interventions

“…Fagopyrum esculentum Rutin Inhibition of the RNA dependent polymerase [58] Cymbopogon winterianus Citronellol ACE-II Inhibitors [59] Torreya nucifera L. Bilobetin, amentoflavonone Inhibition of M pro [60] Lindera aggregate Linderane and linderalactone Inhibition of 3CL pro and spike protein [61] Asparagus…”