Aurasperone A Inhibits SARS CoV-2 In Vitro: An Integrated In Vitro and In Silico Study

Abstract

Several natural products recovered from a marine-derived Aspergillus niger were tested for their inhibitory activity against SARS CoV-2 in vitro. Aurasperone A (3) was found to inhibit SARS CoV-2 efficiently (IC50 = 12.25 µM) with comparable activity with the positive control remdesivir (IC50 = 10.11 µM). Aurasperone A exerted minimal cytotoxicity on Vero E6 cells (CC50 = 32.36 mM, SI = 2641.5) and it was found to be much safer than remdesivir (CC50 = 415.22 µM, SI = 41.07). To putatively highlight its molecular target, aurasperone A was subjected to molecular docking against several key-viral protein targets followed by a series of molecular dynamics-based in silico experiments that suggested Mpro to be its primary viral protein target. More potent anti-SARS CoV-2 Mpro inhibitors can be developed according to our findings presented in the present investigation.

Microbial Natural Products with Antiviral Activities, Including Anti-SARS-CoV-2: A Review

“…In vitro tests show that natural products are as efficacious as commercially available drugs. The IC 50 values for aurasperone A (12.25 µM) were comparable to those for remdesivir (10.11 µM) [152]. Both have a mechanism of action that inhibits M pro , which is essential for the replication and transcription of SARS-CoV-2 [152].…”

“…The IC 50 result was comparable to the IC 50 of the positive control remdesivir, which was 10.11 µM [152]. The in silico analysis revealed that the molecule aurasperone A targets M pro in SARS-CoV-2 [152]. Furthermore, neoechinulin A isolated from Aspergillus fumigatus MR2012 from the Red Sea exhibited an IC 50 value of 0.47 µM against SARS-CoV-2, with a similar target to M pro [153].…”

“…A recent study published in 2022 found that the antimicrobial natural product aurasperone, as listed in Table 1, isolated from Aspergillus niger in the Red Sea tunicate Phallusia nigra, was highly effective against SARS-CoV-2 in vitro, with an IC 50 of 12.25 µM. The IC 50 result was comparable to the IC 50 of the positive control remdesivir, which was 10.11 µM [152]. The in silico analysis revealed that the molecule aurasperone A targets M pro in SARS-CoV-2 [152].…”

“…M pro plays an essential role in the replication and transcription of SARS-CoV-2. There are a number of microbe-produced natural products with the ability to inhibit M pro , including aurasperone A [152]; neoechinulin A [153]; as well as aspulvinone D, M, and R [154].…”

GC-MS profiling of Bauhinia variegata major phytoconstituents with computational identification of potential lead inhibitors of SARS-CoV-2 Mpro

“…The data regarding the biological activity of some selected FDA-approved drugs with SARS-CoV-2 M pro has been collected and correlated with our predicted docking score to show the consistency between the calculated binding score and the reported target activities. The activities of Remdesivir (IC 50 = 10.11 μM/L, pIC 50 = 4.995 μM/L) [ 93 , 94 ], Ritonavir: (IC 50 = 13.7 μM/L, pIC 50 = 4.863 μM/L) [ 95 ]; Favipiravir (IC 50 = 9.60, μM/L, pIC 50 = 5.017, μM/L) [ 96 ], and Imatinib: (IC 50 = 3.24, μM/, pIC 50 = 5.489 μM/L) [ 97 ] were compared with the Glide docking score. The resulted coefficient correlation between docking score and biological activity of these drugs has been obtained.…”