The recent pandemic of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has raised global health concerns. viral 3-chymotrypsin-like cysteine protease (3CLpro) enzyme controls replication and is essential for its life cycle. 3CLpro a proven drug discovery target in the case severe acute respiratory syndrome (SARS-CoV) Middle East (MERS-CoV). Recent studies revealed that genome sequence very similar to SARS-CoV. Therefore, herein, we analysed sequence, constructed 3D homology model,...

The SARS-CoV-2 was confirmed to cause the global pandemic of coronavirus disease 2019 (COVID-19). 3-chymotrypsin-like protease (3CLpro), an essential enzyme for viral replication, is a valid target combat SARS-CoV and MERS-CoV. In this work, we present structure-based study identify potential covalent inhibitors containing variety chemical warheads. targeted Asinex Focused Covalent (AFCL) library screened based on different reaction types were identified. addition, FDA-approved find...

The papain-like protease (PLpro) is vital for the replication of coronaviruses (CoVs), as well escaping innate-immune responses host. Hence, it has emerged an attractive antiviral drug-target. In this study, computational approaches were employed, mainly structure-based virtual screening coupled with all-atom molecular dynamics (MD) simulations to computationally identify specific inhibitors severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PLpro, which can be further developed...

Coronavirus disease 2019 (COVID-19) has affected almost every country in the world by causing a global pandemic with high mortality rate. Lack of an effective vaccine and/or antiviral drugs against SARS-CoV-2, causative agent, severely hampered response to this novel coronavirus. Natural products have long been used traditional medicines treat various diseases, and purified phytochemicals from medicinal plants provide valuable scaffold for discovery new drug leads. In present study, we...

The signal transducer and activator of transcription 3 (STAT3) plays a fundamental role in the growth regulation cellular life. Activation over-expression STAT3 have been implicated many cancers including solid blood tumors other diseases such as liver fibrosis rheumatoid arthritis. Therefore, inhibitors are be coming growing interesting area pharmacological research. Consequently, aim this study is to design novel STAT3-SH3 computationally for reduction fibrosis. Herein, we performed...

KRAS mutations linked with cancer. Flavonoids were docked against G12C and G12D receptors. Abyssinone III, alpha naphthoflavone, beta abyssinone I, II genistin, daidzin showed good docking scores receptors, respectively. The MD simulation data revealed that Rg, RMSD, RMSF, SASA values within acceptable limits. Alpha naphthoflavone binding energies DFT MEP analysis highlighted the nucleophilic electrophilic zones of best-docked flavonoids. A novel avenue for control is made possible by

Alzheimer's disease (AD) ranks as the most prevalent neurodegenerative disorder with dementia and it accounts for more than 70% of all cases. Despite extensive reporting on experimental investigation Datura innoxia (DI) its phytochemical components in treatment AD, urgent need elucidation principle multi-mechanism multi-level AD remains. In this research, molecular docking network pharmacology were used to evaluate active compounds targets DI AD. The obtained from Indian Medicinal Plants,...

Abstract Lung cancer is a disease with high mortality rate and it the number one cause of death globally. Approximately 12–14% non-small cell lung cancers are caused by mutations in KRAS G12C . The most prevalent mutants patients. was first considered undruggable. sotorasib adagrasib recently approved drugs that selectively target , offer new treatment approaches to enhance patient outcomes however drug resistance frequently arises. Drug development challenging, expensive, time-consuming...

Spondias mangifera is a drupaceous fruit popular for its flavour and health advantages. There little scientific knowledge about S. mangifera, despite widespread usage in traditional medicine, the North-Eastern region of India. Inhibiting key carbohydrate hydrolysing enzymes one strategies managing diabetes. Therefore, this study studied antioxidant anti-diabetic properties different fraction extract (SMFFs) from Indian geographical origin by vitro experimental assays silico docking...

Inhibition of Heat-shock protein 90 (Hsp90) is considered an attractive route in fighting against cancer proliferation. Herein, new indene derivatives targeting Hsp90 were synthesized, and biologically evaluated. The series indeno-pyrimidine indeno-pyridine synthesized from the reaction indene-enaminone with various heterocyclic amines active methylene derivatives. Two breast cell lines used to examine compounds vitro for their anticancer activity, namely, MCF-7 MDA-MB231 cells. 8a-c, 17a,...

The Marburg virus (MBV), a deadly pathogen, poses serious threat to world health due the lack of effective treatments, calling for an immediate search targeted and efficient treatments. In this study, we focused on compounds originating from marine fungi in order identify possible inhibitory against (MBV) VP35-RNA binding domain (VP35-RBD) using computational approach. We started with virtual screening procedure Lipinski filter as guide. Based their docking scores, 42 potential candidates...

BACE-1 is an encouraging target for the development of AD therapeutics. However, many inhibitors failed clinical trials due to their non-selectivity towards BACE-2 or adverse effects. Herein, a set 96 benzothiazoles were designed based on structural features Atabecestat and Riluzole find promising selective inhibitor. Out compounds, compound 72 showed comparable binding affinity with as compared Atabecestat, more BACE-2. The docking score found be -7.76 -7.49, respectively, while...

Hypoxanthine guanine phosphoribosyltransferase 1 (HPRT1) is a mutational biomarker and housekeeping human reporter gene that predominantly employed to assess mutation frequencies associated with cancer development. In this study, our purpose was identify potential inhibitors against the hypoxanthine (HPRT) protein encoded by HPRT1 employing an integrated in silico approach. The library of 17,967 phytochemicals (IMPPAT 2.0 database) screened for drug-like properties followed molecular...

SPAK and OSR1 are two protein kinases that have emerged as attractive targets in the discovery of novel antihypertensive agents due to their role regulating electrolyte balance vivo. Herein we report identification an allosteric pocket on highly conserved C-terminal domains these kinases, which influences activity. We also show some known WNK signaling inhibitors bind this site. Using silico screening, identified antiparasitic agent rafoxanide a inhibitor OSR1. Collectively, work will...

The incidence of Hepatocellular Carcinoma (HCC) in Saudi Arabia is not surprising given the relatively high prevalence hepatitis C virus (HCV) infection. Hepatitis also common with a rate 1% to 3% population, which further increases risk HCC. HCC has been increasing recent years, HCV-related accounting for significant proportion cases. Traditional medicine long part Arabian culture, and many medicinal plants have used centuries treat various ailments, including cancer. Following that, this...

The RAS gene family is one of the most frequently mutated oncogenes in human cancers. In KRAS, mutations G12D and G12C are common. Here, 52 iridoids were selected docked against 8AFB (KRAS receptor) using Sotorasib as standard. As per docking interaction data, 6-O-trans-p-coumaroyl-8-O-acetylshanzhiside methyl ester (dock score: -9.9 kcal/mol), 6'-O-trans-para-coumaroyl geniposidic acid -9.6 6-O-trans-cinnamoyl-secologanoside -9.5 Loganic 6'-O-beta-d-glucoside 10-O-succinoylgeniposide -9.4),...

The WNK-SPAK/OSR1 signaling is a complex of serine and threonine protein kinases that involves in the regulation human blood pressure. WNK phosphorylate activate SPAK OSR1 through interaction RFQV motifs with C-terminal domains OSR1. Upon phosphorylation, key ion co-transporters such as Na+-[K+]-2Cl− (NKCC1-2) K+-Cl− (KCC1-4), which are essential for electrolytes balance pressure regulation. Targeting binding site on domain (CTD) has emerged valuable approach to inhibit pathway. Herein, an...

Rift valley fever virus (RVFV) is the causative agent of a viral zoonosis that causes significant clinical burden in domestic and wild ruminants. Major outbreaks occur livestock, contaminated animal products or arthropod vectors can transmit to humans. The RNA-dependent RNA polymerase (RdRp; L protein) RVFV responsible for replication thus an appealing drug target because no effective specific vaccine against this available. current study reported structural elucidation RVFV-L protein by...

Abstract The Rift Valley fever virus (RVFV) is a zoonotic arbovirus and pathogenic to both humans animals. Currently, no proven effective RVFV drugs or licensed vaccine are available for human animal use. Hence, there an urgent need develop treatment options control this viral infection. glycoprotein N (GN), C (GC), nucleocapsid (N) proteins attractive antiviral drug targets due their critical roles in replication. In present study, integrated docking-based virtual screening of more than...

Clostridioides difficile is a gram-positive bacterium which associated with different gastrointestinal related infections, and the numbers of cases to it are continuously increasing in past few years. Owing high prevalence development resistance towards available antibiotics, required develop new therapeutics combat C. infection. The current study was aimed identify novel phytochemicals that could bind inhibits TcdB, an exotoxin for pathogenesis bacteria, hence can be considered as future...