Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly infectious zoonotic virus first reported into the human population in September 2012 on the Arabian Peninsula. The virus causes severe and often lethal respiratory illness in humans with an unusually high fatality rate. The N-terminal domain (NTD) of receptor-binding S1 subunit of coronavirus spike (S) proteins can recognize a variety of host protein and mediates entry into human host cells. Blocking the entry by targeting the S1-NTD of the virus can facilitate the development of effective antiviral drug candidates against the pathogen. Therefore, the study has been designed to identify effective antiviral drug candidates against the MERS-CoV by targeting S1-NTD. Initially, a structure-based pharmacophore model (SBPM) to the active site (AS) cavity of the S1-NTD has been generated, followed by pharmacophore-based virtual screening of 11,295 natural compounds. Hits generated through the pharmacophore-based virtual screening have re-ranked by molecular docking and further evaluated through the ADMET properties. The compounds with the best ADME and toxicity properties have been retrieved, and a quantum mechanical (QM) based density-functional theory (DFT) has been performed to optimize the geometry of the selected compounds. Three optimized natural compounds, namely Taiwanhomoflavone B (Amb23604132), 2,3-Dihydrohinokiflavone (Amb23604659), and Sophoricoside (Amb1153724), have exhibited substantial docking energy >−9.00 kcal/mol, where analysis of frontier molecular orbital (FMO) theory found the low chemical reactivity correspondence to the bioactivity of the compounds. Molecular dynamics (MD) simulation confirmed the stability of the selected natural compound to the binding site of the protein. Additionally, molecular mechanics generalized born surface area (MM/GBSA) predicted the good value of binding free energies (ΔG bind) of the compounds to the desired protein. Convincingly, all the results support the potentiality of the selected compounds as natural antiviral candidates against the MERS-CoV S1-NTD.

The local medicinal plant Rhazya stricta Decne is reviewed for its folkloric medicinal, phytochemical, pharmacological, biological, and toxicological features. R. stricta has been used widely in different cultures for various medical disorders. The phytochemical studies performed on the R. stricta extract revealed many alkaloidal and fatty acid compounds. Moreover, several flavonoid and terpenoid compounds were also detected. Pharmacological activates of R. stricta extracts are approved to possess antimicrobial, antioxidant, anticancer, antidiabetic, and antihypertensive activities. Additionally, R. stricta extract was found to hold biological activates such as larvicidal and phytoremediation activates R. stricta extract was found to be toxic, genotoxic, and mutagenic. R. stricta contains novel phytochemical compounds that have not been investigated pharmacologically. Further research is needed through in vitro and in vivo experiments to pave the road for these compounds for medical, veterinary, and ecological uses.

Coronaviruses emerged three times in the last two decades and became a source of concern globally. Humulus lupulus plant has been used widely in medical science. Our objective in this study was to determine the effects of the crude extract of H. lupulus in inhibiting MERS-CoV and SARS-CoV-2 viruses’ replication in vitro using Vero E6 cell lines and predict the antiviral activity of its identified compounds against the receptor binding (RBD) protein of both viruses in silico. We determined the concentration of the extract that induced less than 50% cell toxicity (CC₅₀), and the antiviral activity based on IC₅₀ and plaque reduction assay. We used molecular docking simulation to predict the potential of known active compounds in H. lupulus to inhibit the RBD protein. H. lupulus extract showed very low toxicity on Vero E6 cells with CC₅₀= 23.25 µg/µL and antiviral activity toward MERS-CoV and SARS-CoV-2 with IC₅₀= 0.18 and 0.9 µg/µL, respectively. The crude extract showed inhibition rate of 84.6% with MERS-CoV and 80% with SARS-CoV-2. In silico analysis predicted the compounds 5′-prenylxanthohumo, xanthogalenol, dehydrocycloxanthohumol hydrate, 6-prenylnaringenin, isoxanthohumol, catechin gallate, epicatechin gallate, 8-prenylnaringenin and xanthohumol to inhibit MERS-CoV and SARS-CoV-2 invasion of host cells by interfering with viral spike protein and the host cell receptor recognition process. Drug likeness and toxicity risk prediction analysis confirmed their capability as potential drugs. Based on our findings, isolation, purification and testing of the suggested active compounds could lead to novel anti-coronavirus drugs.

Influenza viruses have developed resistance to the current classes of drugs, which means they could eventually become more virulent and cause more mortality and hospitalization. Our study aims to investigate the antiviral activity of Rhazya stricta Decne leaves extract in vitro and search for new promising drugs from R. stricta identified compounds in silico. The study was performed in vitro by utilizing Madin-Darby Canine Kidney cell line (MDCK) as a substrate for the influenza virus and estimating the inhibition performance of the plant leaves extract. Additionally, in silico screening was conducted to explore the antiviral activity of R. stricta phytochemicals. We investigated the cytotoxicity of R. stricta leaves extract and its antiviral activity against influenza virus (A/Puerto Rico/8/34 (H1N1)) using the MTT assay. The mode of action of the plant leaves extract during the viral life cycle was tested using time-of-addition assay. In silico analyses were performed, including molecular docking, drug-likeness analysis, and toxicity risk assessment, to state the leading compounds to be developed into an anti-influenza virus drug. The 50% cytotoxicity concentration of the leaves extract was CC50: 184.6 µg/mL, and the 50% inhibition concentration was CI50: 19.71 µg\mL. The time of addition assay revealed that R. stricta leaves extract exerted its activity in the late step of the influenza virus replication cycle. In comparison to Oseltamivir, the leading compounds showed better binding affinity and can be developed into oral drugs with low toxicity risk. Isolation and purification of the leading compounds and testing their antiviral activity in vitro and in vivo are required.

Melissa officinalis is a perennial medicinal plant traditionally used for its diverse biological activities, including antiviral properties. This study investigates the antiviral efficacy of various extracts, including water, acetone, alkaloid, non-alkaloid, ethanol, and methanol extracts, against influenza A (H1N1), SARS-CoV-2, and MERS-CoV. The water extract demonstrated significant inhibitory effects on SARS-CoV-2 (IC₅₀ = 421.9 µg/mL) and MERS-CoV (IC₅₀ = 222.1 µg/mL) in Vero E6 cells (an African green monkey kidney cell line), with a CC₅₀ of 4221 µg/mL, indicating a favorable selectivity index. Additionally, it exhibited strong activity against H1N1 in Madin-Darby canine kidney cell line (MDCK cells) (IC₅₀ = 57.30 µg/mL, CC₅₀ = 3073 µg/mL). Among all the extracts, the methanol extract showed the highest antiviral activity. It has IC₅₀ = 2.549 µg/ml and selectivity index (SI) = 230 against H1N1.While it showed IC₅₀ = 10.83 µg/ml against SARS-CoV-2 and 9.82 µg/ml against MERS-CoV with SI values of 54.2 and 59.77, respectively. Molecular docking studies revealed that 5-Methyl-5 H-naphtho[2,3-c]carbazole,7 H-Dibenzo[b, g]carbazole, 7-methyl, hesperidin, luteolin-7-glucoside-3′-glucuronide, Melitric acid A, and other compounds exhibited high binding affinities to the receptor-binding domains (RBDs) of SARS-CoV-2 and MERS-CoV spike glycoproteins, suggesting their potential to interfere with viral entry. Furthermore, GC-MS-identified bioactive compounds, including docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), paromomycin, and phenolic acids, demonstrated additional antiviral potential. These results underscore the potential of M. officinalis extracts as natural antiviral agents, offering a foundation for further in vitro and in vivo validation and potential therapeutic applications against respiratory viral infections, including coronaviruses and influenza viruses.

The Middle Eastern prevalence of sickle cell anemia, a genetic disorder that affects red blood cells, necessitates additional research. On a molecular level, we sought to identify and sort the oral microbiota of healthy individuals and those with sickle cell anemia. Furthermore, it is crucial to comprehend how changes in the genetic makeup of the oral microbiota impact the state of sickle cell anemia. Using next-generation sequencing, the 16S rRNA amplicon was examined using saliva samples from 36 individuals with sickle cell anemia and healthy individuals. These samples were obtained from sickle cell anemia patients (18 samples) and healthy control participants (controls, 18 samples). Various analyses are conducted using bioinformatic techniques to identify distinct species and their relative abundance. Streptococcus, followed by Fusobacterium nucleatum, Prevotella, and Veillonella were the most prevalent genera of bacteria in the saliva of the SCA and non-SCA individuals according to our findings. Rothia mucilaginosa, Prevotella scoposa, and Veillonella dispar species were the dominant species in both sickle cell anemia and non-sickle cell anemia subjects. Streptococcus salivarius, Actinomyces graevenitzii, Actinomyces odontolyticus, and Actinomyces georgiae spp. were the most prevalent bacterial spp. in the studied SCA cases. The sequencing of the 16S rRNA gene yielded relative abundance values that were visualized through a heatmap analysis. Alterations in the oral microflora’s constitution can significantly affect the susceptibility of sickle cell anemia patients to develop more severe health complications. Salivary diagnosis is a potential tool for predicting and preventing oral microbiome-related diseases in the future.