The workshops on computational applications in secondary metabolite discovery (CAiSMD).

We report the outcomes of the second session of the free online open-access workshop "Computational Applications in Secondary Metabolite Discovery (CAiSMD) 2022" that took place from 09 to 11 March 2022. The first session was held from 08 to 10 March 2021 and drew the attention of many early career scientists from academia and industry. The 23 invited speakers of this year's workshop also came from academia and industry and 222 registered participants from five continents (Africa, Asia, Europe, South, and North America) took part in the workshop.

Predictive immunoinformatics reveal promising safety and anti-onchocerciasis protective immune response profiles to vaccine candidates (Ov-RAL-2 and Ov-103) in anticipation of phase I clinical trials.

Onchocerciasis (river blindness) is a debilitating tropical disease that causes significant eye and skin damage, afflicting millions worldwide. As global efforts shift from disease management to elimination, vaccines have become crucial supplementary tools. The Onchocerciasis Vaccine for Africa (TOVA) Initiative was established in 2015, to advance at least one vaccine candidate initially targeting onchocerciasis in infants and children below 5 years of age, through Phase I human trials by 2025.

Drug repositioning identifies salvinorin A and deacetylgedunin (DCG) enriched plant extracts as novel inhibitors of Mpro, RBD-ACE2 and TMPRRS2 proteins.

The coronavirus disease 2019 (COVID-19) has spread worldwide with severe health, social, and economic repercussions. Although vaccines have significantly reduced the severity of symptoms and deaths, alternative medications derived from natural products (NPs) are vital to further decrease fatalities, especially in regions with low vaccine uptake. When paired with the latest computational developments, NPs, which have been used to cure illnesses and infections for thousands of years, constitute a renewed resource for drug discovery.

A nanoscale study of the structure and electrical response of Sepia eumelanin.

Eumelanin, the brown-black member of the melanin biopigment family, is a prototype material for sustainable (green) organic electronics. Sepia eumelanin (Sepia) is a type of biosourced eumelanin extracted from the ink sac of cuttlefish. Electron microscopy and scanning probe microscopy images of Sepia show distinguishable near spherical granules with diameters of about 150-200 nm.

Archaic connectivity between the sulfated heparan sulfate and the herpesviruses - An evolutionary potential for cross-species interactions.

The structural diversity of metazoic heparan sulfate (HS) composed of unique sulfated domains is remarkably preserved among various vertebrates and invertebrate species. Interestingly the sulfated moieties of HS have been known as the key determinants generating extraordinary ligand binding sites in the HS chain to regulate multiple biological functions and homeostasis. One such ligand for 3-O sulfation in the HS chain is a glycoprotein D (gD) from an ancient herpesvirus, herpes simplex virus (HSV).

Neuroprotective potential of cinnamoyl derivatives against Parkinson's disease indicators in Drosophila melanogaster and in silico models.

Parkinson's disease (PD) is a movement disorder resulting from the loss of dopaminergic neurons over time. While there is no cure for PD, available conventional therapies aid to manage the motor symptoms. Natural products (NPs) derived from plants are among the most potent alternative therapies for PD.

Hydrophobic π-π stacking interactions and hydrogen bonds drive self-aggregation of luteolin in water.

Luteolin is a flavonoid obtained from different plant species. It is known for its versatile biological activities. However, the beneficial effects of luteolin have been limited to small concentrations as a result of poor water solubility.

Finding alternatives to 5-fluorouracil: application of ensemble-based virtual screening for drug repositioning against human thymidylate synthase.

5-fluorouracil and analogs are used in the treatment of many solid tumours. However, there are many cases of resistance and high toxicity associated with 5-fluorouracil chemotherapy. Repurposing FDA drugs against human thymidylate synthase revealed a number of FDA drugs that have a potential to be further developed for the treatment of various cancers for which 5-fluorouracil and analogs have been used for chemotherapy.

Cation-π interactions drive hydrophobic self-assembly and aggregation of niclosamide in water.

The beneficial medicinal effects of niclosamide have been reported to be hampered by poor aqueous solubility and so a higher concentration dosage is required. In this work, we have studied the aggregation properties of niclosamide in water by varying the number of monomers. We have employed all-atom classical molecular dynamics simulation in order to explore such properties.

study of the inhibition of SARS-COV-2 viral cell entry by neem tree extracts.

The outbreak of COVID-19, caused by SARS-COV-2, is responsible for higher mortality and morbidity rates across the globe. Until now, there is no specific treatment of the disease and hospitalized patients are treated according to the symptoms they develop. Efforts to identify drugs and/or vaccines are ongoing processes.

Relaxed complex scheme and molecular dynamics simulation suggests small molecule inhibitor of human TMPRSS2 for combating COVID-19.

As the coronavirus disease 19 (COVID-19) pandemic continues to pose a health and economic crisis worldwide, the quest for drugs and/or vaccines against the virus continues. The human transmembrane protease serine 2 (TMPRSS2) has attracted attention as a target for drug discovery, as inhibition of its catalytic reaction would result in the inactivation of the proteolytic cleavage of the SARS-CoV-2 S protein. As a result, the inactivation prevents viral cell entry to the host's cell.

Computational Applications in Secondary Metabolite Discovery (CAiSMD): an online workshop.

We report the major conclusions of the online open-access workshop "Computational Applications in Secondary Metabolite Discovery (CAiSMD)" that took place from 08 to 10 March 2021. Invited speakers from academia and industry and about 200 registered participants from five continents (Africa, Asia, Europe, South America, and North America) took part in the workshop. The workshop highlighted the potential applications of computational methodologies in the search for secondary metabolites (SMs) or natural products (NPs) as potential drugs and drug leads.

Luteolin: a blocker of SARS-CoV-2 cell entry based on relaxed complex scheme, molecular dynamics simulation, and metadynamics.

Natural products have served human life as medications for centuries. During the outbreak of COVID-19, a number of naturally derived compounds and extracts have been tested or used as potential remedies against COVID-19. Tetradenia riparia extract is one of the plant extracts that have been deployed and claimed to manage and control COVID-19 by some communities in Tanzania and other African countries.

Accommodating receptor flexibility and free energy calculation to reduce false positive binders in the discovery of natural products blockers of SARS-COV-2 spike RBD-ACE2 interface.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), which causes coronavirus disease-19 (COVID-19) has caused more than 2 million deaths around the globe. The high transmissibility rate of the disease is related to the strong interaction between the virus spike receptor-binding domain (RBD) and the human angiotensin-converting enzyme 2 (ACE2) as documented in several reports. In this study, using state-of-the-art computational methods, natural products were screened and their molecular mechanism to disrupt spike RBD-ACE2 recognition was evaluated.

Molecular dynamics simulation of bioactive compounds of leaf extract as DNA gyrase inhibitor.

Medicinal plants have served humans as medicine for centuries. (L.) (Ashwagandha) leaf extract is traditionally used in managing and treating bacterial infections.

Structural characterization of cassava linamarase-linamarin enzyme complex: an integrated computational approach.

Cassava linamarase is a hydrolyzing enzyme that belongs to a glycoside hydrolase family 1 (GH1). It is responsible for breaking down linamarin to toxic cyanide. The enzyme provides a defensive mechanism for plants against herbivores and has various applications in many fields.

Solvent effects on host-guest residence time and kinetics: further insights from metadynamics simulation of Toussaintine-A unbiding from chitosan nanoparticle.

Solvents play an important role in host-guest intermolecular interactions. The kinetics and residence time of Toussaintine-A (TouA) unbinding from chitosan was investigated by means of well-tempered metadynamics and thermodynamic integration using two solvents, polar aprotic (DMSO), and polar protic (water). The kinetic rates were found to be strongly dependent on the solvent polarity; hence, the unbinding rate proceeded much faster in DMSO compared to water.

Ensemble-based screening of natural products and FDA-approved drugs identified potent inhibitors of SARS-CoV-2 that work with two distinct mechanisms.

The recent outbreak of SARS-CoV-2 is responsible for high morbidity and mortality rate across the globe. This requires an urgent identification of drugs and other interventions to overcome this pandemic. Computational drug repurposing represents an alternative approach to provide a more effective approach in search for COVID-19 drugs.

Crystal structure and Hirshfeld surface analysis of ()-4-{2,2-di-chloro-1-[(3,5-di-methyl-phen-yl)diazen-yl]ethen-yl}-,-di-methyl-aniline.

In the title compound, CHClN, the planes of the benzene rings subtend a dihedral angle of 77.07 (10)°. In the crystal, mol-ecules are associated into inversion dimers short Cl⋯Cl contacts [3.

A computational study on the role of water and conformational fluctuations in Hsp90 in response to inhibitors.

Molecular chaperone Heat Shock Protein 90 (Hsp90) represents an interesting chemotherapeutic target for cancer treatments as it plays a role in cancer proliferation. Thus, continued effort to identify novel inhibitors of this target is an important task. Drug design using computational approach has gained significant attention in recent years.

Polyamidoamine Dendrimers for Enhanced Solubility of Small Molecules and Other Desirable Properties for Site Specific Delivery: Insights from Experimental and Computational Studies.

Clinical applications of many small molecules are limited due to poor solubility and lack of controlled release besides lack of other desirable properties. Experimental and computational studies have reported on the therapeutic potential of polyamidoamine (PAMAM) dendrimers as solubility enhancers in pre-clinical and clinical settings. Besides formulation strategies, factors such as pH, PAMAM dendrimer generation, PAMAM dendrimer concentration, nature of the PAMAM core, special ligand and surface modifications of PAMAM dendrimer have an influence on drug solubility and other recommendable pharmacological properties.

Synthesis of Polyamidoamine Dendrimer for Encapsulating Tetramethylscutellarein for Potential Bioactivity Enhancement.

The biomedical potential of flavonoids is normally restricted by their low water solubility. However, little has been reported on their encapsulation into polyamidoamine (PAMAM) dendrimers to improve their biomedical applications. Generation four (G4) PAMAM dendrimer containing ethylenediaminetetraacetic acid core with acrylic acid and ethylenediamine as repeating units was synthesized by divergent approach and used to encapsulate a flavonoid tetramethylscutellarein (TMScu, 1) to study its solubility and in vitro release for potential bioactivity enhancement.