This present study reports some natural products and one hydroxamic acid synthetic compound which were previously reported as matrix metalloproteinase-9 (MMP-9) inhibitors to be evaluated for their inhibition toward severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) 3-chymotrypsin-like protease (3CLpro). This enzyme is one of the proteins responsible for this coronaviral replication. Two herbal methanolic extracts i.e.,
Averrhoa carambola
leaves and
Ageratum conyzoides
aerial part demonstrate >50% inhibition at 1000 µg/mL. Interestingly, apigenin, one of flavonoids, demonstrates 92% inhibition at 250 µg/mL (925 µM) as well as hydroxamic acid compound,
N
-isobutyl-
N
-(4-methoxyphenylsulfonyl)glycyl hydroxamic acid (NNGH), which shows 69% inhibition at 100 µM. The
in vitro
results are supported by the docking studies revealing that the binding mode of both compounds is mainly by interacting with GLU166 residue in the hydrophobic pocket of the 3CLpro. Pharmacophore mapping further supported the results by confirming that the
in vitro
activities of both compounds are due to their pharmacophore features employing hydrogen bond acceptor (HBA), hydrogen bond donor (HBD) and hydrophobic. Gas Chromatography-Mass Spectrometry (GC–MS) analysis reported chromene compounds in
Ageratum conyzoides
aerial part methanolic extract are potential to be this enzyme inhibitor candidate. These all results reflect their potencies to be SARS-CoV-2 inhibitors through 3CLpro inhibition mechanism.
Resorcinol and 4-n-butyl resorcinol have been used to improve skin health. However, these two compounds were unstable due to the oxidation process. Lipid nanoparticle formulation strategies were reported as the solution to overcome the stability problem for both resorcinol and 4-n-butyl resorcinol. Nevertheless, it is important to determine the content of resorcinol and 4-n-butyl resorcinol in lipid nanoparticle formulation. Aiming to develop the analytical method for resorcinol and 4-n-butyl resorcinol determination, a response surface methodology (RSM) was applied in the HPLC optimization stage. An optimized HPLC condition was obtained by generating a Box-Behnken design followed by multiple response analysis. It was obtained that optimized HPLC conditions due to the predictive multiple response optimization were methanol percentage of 50.0%, acetonitrile percentage of 18.1%, and flow rate of 0.6 mL min–1. This optimized condition was successfully applied and met the requirements of the system suitability test. Quantitative estimation was performed and resulted that the resorcinol and 4-n-butyl resorcinol content in lipid nanoparticles were 70.37 ± 0.47 and 95.07 ± 0.80 µg mL–1, respectively.
2-Phenoxyacetamide group has been identified as one of markers in the discovery and development of SARS-CoV-2 antiviral agent through its main protease (M
pro
) inhibition pathway. This study aims to study a series of 2-phenoxyacetamide derivatives using
in silico
method toward SARS-CoV-2 M
pro
as the protein target. The study was initiated by employing structure-based pharmacophore to virtually screen and to select the ligands, which have the best fit score (hits) along with the common pharmacophore features being matched. The result shows that from the 11 ligands designed, four ligands are selected as the hits by demonstrating fit score in the range of 56.20 to 65.53 to the pharmacophore model, employing hydrogen bond acceptor (HBA) and hydrophobic (H) as the common features. The hits were then docked into the binding site of the M
pro
to see the binding mode of the corresponding hits as well as its affinity. The docking results free energy of binding (ΔG
bind
) of the hits are in agreement with the pharmacophore fit score, in the range of -6.83 to -7.20 kcal/ mol. To gain the information of the hits as a potential drug to be developed, the
in silico
study was further proceed by predicting the mutagenic potency, toxicity and pharmacokinetic profiles. Based on the efficiency percentage, all hits meet the criteria as drug candidates by showing 84-88% leading to a conclusion that 2-phenoxyacetamide derivatives are beneficial to be marked as the lead compound for SARS-CoV-2 M
pro
inhibitor.
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