bims-antpol 2024-07-21 papers

Issue of 2024–07–21
three papers selected by
Rick Sheridan, EMSKE Phytochem

BMC Complement Med Ther. 2024 Jul 19. 24(1): 274

Exploring the therapeutic potential of Thai medicinal plants: in vitro screening and in silico docking of phytoconstituents for novel anti-SARS-CoV-2 agents.

Bussayarat Maikhunthod, Sukanya Chaipayang, Akanitt Jittmittraphap, Narin Thippornchai, Pakpoom Boonchuen, Panlada Tittabutr, Griangsak Eumkeb, Sahachai Sabuakham, Thanyada Rungrotmongkol, Panupong Mahalapbutr, Pornsawan Leaungwutiwong, Neung Teaumroong, Waraporn Tanthanuch.

BACKGROUND: The high virulence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for coronavirus disease 2019 (COVID-19), has triggered global health and economic concerns. The absence of specific antiviral treatments and the side effects of repurposed drugs present persistent challenges. This study explored a promising antiviral herbal extract against SARS-CoV-2 from selected Thai medicinal plants based on in vitro efficacy and evaluated its antiviral lead compounds by molecular docking.
METHODS: Twenty-two different ethanolic-aqueous crude extracts (CEs) were rapidly screened for their potential activity against porcine epidemic diarrhea virus (PEDV) as a surrogate using a plaque reduction assay. Extracts achieving ≥ 70% anti-PEDV efficacy proceeded to the anti-SARS-CoV-2 activity test using a 50% tissue culture infectious dose method in Vero E6 cells. Molnupiravir and extract-free media served as positive and negative controls, respectively. Potent CEs underwent water/ethyl acetate fractionation to enhance antiviral efficacy, and the fractions were tested for anti-SARS-CoV-2 performance. The fraction with the highest antiviral potency was identified using liquid chromatography-high-resolution mass spectrometry (LC-HRMS). Molecular docking analyses of these compounds against the main protease (Mpro) of SARS-CoV-2 (6LU7) were performed to identify antiviral lead molecules. The top three hits were further evaluated for their conformational stability in the docked complex using molecular dynamics (MD) simulation.
RESULTS: The water fraction of mulberry (Morus alba Linn.) leaf CE (WF-MLCE) exhibited the most potent anti-SARS-CoV-2 efficacy with low cytotoxicity profile (CC50 of ~ 0.7 mg/mL), achieving 99.92% in pre-entry mode and 99.88% in postinfection treatment mode at 0.25 mg/mL. Flavonoids and conjugates were the predominant compounds identified in WF-MLCE. Molecular docking scores of several flavonoids against SARS-CoV-2 Mpro demonstrated their superior antiviral potency compared to molnupiravir. Remarkably, myricetin-3-O-β-D-galactopyranoside, maragrol B, and quercetin 3-O-robinobioside exhibited binding energies of ~ - 9 kcal/mol. The stability of each ligand-protein complex of these compounds with the Mpro system showed stability during MD simulation. These three molecules were pronounced as antiviral leads of WF-MLCE. Given the low cytotoxicity and high antiviral potency of WF-MLCE, it holds promise as a candidate for future therapeutic development for COVID-19 treatment, especially considering its economic and pharmacological advantages.

Keywords: Anti-SARS-CoV-2; COVID-19; Flavonoids; LC–HRMS; Molecular docking; Mulberry; Thai medicinal plants

DOI: https://doi.org/10.1186/s12906-024-04586-z

J Ethnopharmacol. 2024 Jul 15. pii: S0378-8741(24)00880-8. [Epub ahead of print] 118581

Investigating the antiviral activity of Erigeron annuus (L.) Pers extract against RSV and examining its active components.

Xiaoxu Zhang, Shengjun Zhou, Hongyu Yu, Yuzhuo Zhu, Li Zhang, Feng Jv Niu, Changzheng Zhou, Xinhuan Wan, Lina Gao.

ETHNOPHARMACOLOGICAL RELEVANCE: The plants in the genus Erigeron are known to exhibit antiviral activities, including those against the respiratory syncytial virus (RSV). In traditional medicine Erigeron annuus (L.) Pers (EA) has been used in the treatment of pulmonary diseases and acute infectious hepatitis.
AIM OF THIS STUDY: The aim of this study is to determine the optimum extraction method to produce the most potent anti-RSV extract, elucidate its mode and mechanisms of antiviral activity in both in vitro and in vivo models, and identify the chemical structures of the bioactive compounds.
MATERIALS AND METHODS: The whole plant of EA was extracted with ethyl acetate, methanol, ethanol, water, aqueous methanol (60, 80% and 100%) and aqueous ethanol (50, 75% and 95%) using maceration, reflux, and ultrasound-assisted extraction methods. The antiviral activities of the extracts were determined in vitro. The in vitro antiviral activities of the extracts were determined using Hep-2 cells. Four in vitro experiments were performed to determine the mode of antiviral activity of the most active extract, ethyl acetate fraction (EAE) of Erigeron annuus whole plant extract prepared by refluxing with 50% ethanol, by examining its ability to inactivate the virus directly, inhibit viral adsorption and penetration, inhibit viral replication and preventive effect. The effect of temperature and duration of treatment on these modes of action was also determined. The antiviral activity of the EAE was also assessed in vivo in a mouse model. The lung index, viral load, and lung tissue histology were measured. qRT-PCR and ELISA studies were performed to determine the expression of key genes (TLR-3 and TLR-4) and proteins (IL-2, IFN-γ, and TNF-α) related to RSV infection. The most active antiviral compound was isolated using chromatography techniques, and its chemical structure was identified through electrospray triple quadrupole mass spectroscopy and nuclear magnetic resonance spectroscopy.
RESULTS: The EAE was the most active on RSV. In vitro experiments showed that the antiviral activity of EAE is via direct inactivation, inhibition of entry, and inhibition of the proliferation of the virus. In vivo experiments showed that the EAE effectively inhibited the proliferation of RSV in the lungs and alleviated the lung tissue lesions in RSV-infected mice. The antiviral activity of the EAE is mediated by downregulating the expression of TLR3 and TLR4 in the lung, upregulating the expression of IL-2 and IFN-γ, and downregulating the expression of TNF-α. Apigenin 7-O-methylglucuronide was found to be a major bioactive compound in EAE.
CONCLUSIONS: The results of this study confirmed the antiviral activity of EA by inactivating, inhibiting the entry, and inhibiting the proliferation of RSV. The activity is mediated by regulating the immunity and inflammatory mediators. Apigenin 7-O-methylglucuronide is the bioactive compound present in EA.

Keywords: Apigenin 7-O-methylglucuronide; Cytokines; Erigeron annuus (L.) Pers; Respiratory syncytial virus (RSV); Toll-like receptors

DOI: https://doi.org/10.1016/j.jep.2024.118581

Biochem Biophys Res Commun. 2024 Jul 11. pii: S0006-291X(24)00929-X. [Epub ahead of print]730 150393

Inhibition of early RNA replication in Chikungunya and Dengue virus by lycorine: In vitro and in silico studies.

Tanvi Agrawal, Gazala Siddqui, Ridhima Dahiya, Aanchal Patidar, Upasna Madan, Supratik Das, Shailendra Asthana, Sweety Samal, Amit Awasthi.

Arboviruses such as chikungunya virus (CHIKV) and dengue virus (DENV) collectively afflict millions of individuals worldwide particularly in endemic countries like India, leading to substantial morbidity and mortality. With the lack of effective vaccines for both CHIKV and DENV in India, the search for antiviral compounds becomes paramount to control these viral infections. In line with this, our investigation was focused on screening natural compounds for their potential antiviral activity against CHIKV and DENV. Using different assays, including plaque assay, immunofluorescence, and reverse transcription-quantitative real-time PCR (qRT-PCR), out of 109 natural compounds tested, we confirmed lycorine's in vitro antiviral activity against CHIKV and DENV at low micromolar concentrations in different cell types. Time of addition assays indicated that lycorine does not impede viral entry. Additionally, qRT-PCR results along with time of addition assay suggested that lycorine interferes with the synthesis of negative strand viral RNA. Molecular docking analysis was done to understand the mode of inhibition of viral replication. The results revealed that the most likely binding site with the highest binding affinity of lycorine, was at the palm and finger domains, in the vicinity of the catalytic site of CHIKV and DENV RNA-dependent RNA polymerase (RdRp). Collectively, our data underscores the potential of lycorine to be developed as a direct acting inhibitor for DENV and CHIKV, addressing the critical need of requirement of an antiviral in regions where these viruses pose significant public health threats.

Keywords: Antiviral; Chikungunya; Dengue; Lycorine; Natural product; RNA dependent RNA polymerase

DOI: https://doi.org/10.1016/j.bbrc.2024.150393