Adapting beyond borders: Insights from the 19th Student Council Symposium (SCS2023), the first hybrid ISCB Student Council global event.

Summary: The 19th ISCB Student Council Symposium (SCS2023) organized by ISCB-SC adopted a hybrid format for the first time, allowing participants to engage in-person in Lyon, France, and virtually via an interactive online platform. The symposium prioritized inclusivity, featuring on-site sessions, poster presentations, and social activities for in-person attendees, while virtual participants accessed live sessions, interactive Q&A, and a virtual exhibit hall. Attendee statistics revealed a global reach, with Europe as the major contributor. SCS2023's success in bridging in-person and virtual experiences sets a precedent for future events in Computational Biology and Bioinformatics. Availability and Implementation: The details of the symposium, speaker information, schedules, and accepted abstracts, are available in the program booklet (https://doi.org/10.5281/zenodo.8173977). For organizers interested in adopting a similar hybrid model, it would be beneficial to have access to details regarding the online platform used, the types of sessions offered, and the challenges faced. Future iterations of SCS can address these aspects to further enhance accessibility and inclusivity.

Intronic Variants of the Angiotensin-Converting Enzyme 2 Gene Modulate Plasma ACE2 Levels and Possibly Confer Protection against Severe COVID-19.

Membrane-bound angiotensin-converting enzyme 2 (ACE2) receptor acts as the entry point for the novel coronavirus, SARS-CoV-2. Polymorphisms in the ACE2 gene may alter viral binding, regulate the expression of ACE2, and thus, affect disease severity. In this study, 68 COVID-19 patients with varying degrees of severity and 40 healthy controls were enrolled. The genetic landscape of the ACE2 gene was explored by whole exome sequencing of 29 individuals, and specific regions of ACE2 were analyzed for the rest of the participants via PCR, followed by barcode-tagged sequencing. The mean soluble ACE2 level in the plasma of healthy controls and patients did not vary significantly but was higher in the patient group (3.77 ± 1.55 ng/mL vs. 3.94 ± 1.42 ng/mL). Analysis of exon 1, exon 2, and exon 8 of the ACE2 gene revealed that these regions are highly conserved in our population. Investigation of exon 11 and its flanking intronic region revealed that deletions in a stretch of 18T nucleotides in the noncoding region significantly decrease ACE2 levels in plasma, as individuals harboring wild-type variants had higher plasma ACE2 levels compared to those harboring T1del, T2del, and T3del variants. However, the intronic variants were not found to be significantly associated with disease severity.

Most frequently harboured missense variants of hACE2 across different populations exhibit varying patterns of binding interaction with spike glycoproteins of emerging SARS-CoV-2 of different lineages.

Since the emergence of SARS-CoV-2 at Wuhan in the Hubei province of China in 2019, the virus has accumulated various mutations, giving rise to many variants. According to the combinations of mutations acquired, these variants are classified into lineages and greatly differ in infectivity and transmissibility. In 2021 alone, a variant of interest (VoI) Mu (B.1.621), as well as, variants of concern (VoC) Delta (B.1.617.2) and Omicron (BA.1, BA.2) and later in 2022, BA.4, BA.5, and BA.2.12.1 have emerged. Since then, the world has seen prominent surges in the rate of infection during short periods of time. However, not all populations have suffered equally, which suggests a possible role of host genetic factors. Here, we investigated the strength of binding of the spike glycoprotein receptor-binding domain (RBD) of the SARS-CoV-2 variants: Mu, Delta, Delta Plus (AY.1), Omicron sub-variants BA.1, BA.2, BA.4, BA.5, and BA.2.12.1 with the human angiotensin-converting enzyme 2 (hACE2) missense variants prevalent in major populations. In this purpose, molecular docking analysis, as well as, molecular dynamics simulation was performed of the above-mentioned SARS-CoV-2 RBD variants with the hACE2 containing the single amino acid substitutions prevalent in African (E37K), Latin American (F40L), non-Finnish European (D355 N), and South Asian (P84T) populations, in order to predict the effects of the lineage-defining mutations of the viral variants on receptor binding. The effects of these mutations on protein stability were also explored. The protein-protein docking and molecular dynamics simulation analyses have revealed variable strength of attachment and exhibited altered interactions in the case of different hACE2-RBD complexes. In vitro studies are warranted to confirm these findings which may enable early prediction regarding the risk of transmissibility of newly emerging variants across different populations in the future.

Toward the Identification of Natural Antiviral Drug Candidates against Merkel Cell Polyomavirus: Computational Drug Design Approaches.

Merkel cell carcinoma (MCC) is a rare form of aggressive skin cancer mainly caused by Merkel cell polyomavirus (MCPyV). Most MCC tumors express MCPyV large T (LT) antigens and play an important role in the growth-promoting activities of oncoproteins. Truncated LT promotes tumorigenicity as well as host cell proliferation by activating the viral replication machinery, and inhibition of this protein in humans drastically lowers cellular growth linked to the corresponding cancer. Our study was designed with the aim of identifying small molecular-like natural antiviral candidates that are able to inhibit the proliferation of malignant tumors, especially those that are aggressive, by blocking the activity of viral LT protein. To identify potential compounds against the target protein, a computational drug design including molecular docking, ADME (absorption, distribution, metabolism, and excretion), toxicity, molecular dynamics (MD) simulation, and molecular mechanics generalized Born surface area (MM-GBSA) approaches were applied in this study. Initially, a total of 2190 phytochemicals isolated from 104 medicinal plants were screened using the molecular docking simulation method, resulting in the identification of the top five compounds having the highest binding energy, ranging between -6.5 and -7.6 kcal/mol. The effectiveness and safety of the selected compounds were evaluated based on ADME and toxicity features. A 250 ns MD simulation confirmed the stability of the selected compounds bind to the active site (AS) of the target protein. Additionally, MM-GBSA analysis was used to determine the high values of binding free energy (ΔG bind) of the compounds binding to the target protein. The five compounds identified by computational approaches, Paulownin (CID: 3084131), Actaealactone (CID: 11537736), Epigallocatechin 3-O-cinnamate (CID: 21629801), Cirsilineol (CID: 162464), and Lycoricidine (CID: 73065), can be used in therapy as lead compounds to combat MCPyV-related cancer. However, further wet laboratory investigations are required to evaluate the activity of the drugs against the virus.