Piton: Investigating the Controllability of a Wearable Telexistence Robot.

The COVID-19 pandemic impacted collaborative activities, travel, and physical contact, increasing the demand for real-time interactions with remote environments. However, the existing remote communication solutions provide limited interactions and do not convey a high sense of presence within a remote environment. Therefore, we propose a snake-shaped wearable telexistence robot, called Piton, that can be remotely used for a variety of collaborative applications. To the best of our knowledge, Piton is the first snake-shaped wearable telexistence robot. We explain the implementation of Piton, its control architecture, and discuss how Piton can be deployed in a variety of contexts. We implemented three control methods to control Piton: HM-using a head-mounted display (HMD), HH-using an HMD and hand-held tracker, and FM-using an HMD and a foot-mounted tracker. We conducted a user study to investigate the applicability of the proposed control methods for telexistence, focusing on body ownership (Alpha IVBO), mental and physical load (NASA-TLX), motion sickness (VRSQ), and a questionnaire to measure user impressions. The results show that both the HM and HH provide relevantly high levels of body ownership, had high perceived accuracy, and were highly favored, whereas the FM control method yielded the lowest body ownership effect and was least favored. We discuss the results and highlight the advantages and shortcomings of the control methods with respect to various potential application contexts. Based on our design and evaluation of Piton, we extracted a number of insights and future research directions to deepen our investigation and realization of wearable telexistence robots.

Extensive Crystallographic Fragment-Based Approach to Design SARS CoV2 3CLpro Main Protease Inhibitors and Related Metadata (preprint)

3CLpro is a vital protein for the SARS-CoV-2 replications and its inhibition using small molecules is a bona fide approach used to develop new drugs against the virus. In this study, a comprehensive crystallography-guided fragment-based drug discovery approach was employed to design new inhibitors for SARS-CoV-2 3CLpro. Protein Data Bank was explored to find small molecules cocrystallized with SARS-CoV-2 3CLpro. The fragments sitting in the binding pocket (87) were interactively coupled using various linkers with the intention to get molecules having the same orientation as those of the constituting fragments. In total, 1251 couples were prepared and converted to maximum possible stereoisomers using LigPrep for screening using Glide (standard precision and extra precision), AutoDock Vina, and Prime MMGBSA. Top 22 hits having conformations similar to their cocrystallized fragments were selected for MD simulation on Desmond. MD simulation suggested that 15 hits had conformations very close to their constituting fragments. Results indicated that these hits were computationally reliable and could be considered for further development. This suggests that the study could provide a benchmark starting point for the further design of SARS-CoV-2 3CLpro inhibitors with improved binding (data provided).

Identification of Novel Human USP2 Inhibitor: Might Involve in SARS-CoV-2 Papain-Like (PLpro) Protease Deubiquitination Activity (preprint)

The ubiquitin-specific protease 2 (USP) belongs to the family of deubiquitinases and plays a critical role in tumors cells’ survival and therefore signifies an important therapeutic target. Previous studies have indicated promising efficacies of potent human USP2 inhibitors including, thiopurine analogues against SARS-CoV papain-like proteases (PLpro). The PLpro have significant functional implications in the innate immune response during SARS-CoV-2 infection and considered an important antiviral target. Both proteases share strikingly similar USP fold with right-handed thumb–palm–fingers structural scaffold and conserved catalytic triad Cys-His-Asp/Asn. In this urgency situation of COVID-19 outbreak, there is a lack of in-vitro facilities readily available to test SARS-CoV-2 inhibitors in whole-cell assays. Therefore, we adopted an alternate route to identify potential USP2 inhibitor through integrated structure-based virtual screening efforts. After a subsequent virtual screening protocol, the best compounds were selected and tested. The compound Z93 showed significant IC50 value against Jurkat (9.67 µM) and MOTL-4 cells (11.8 µM). The binding mode of Z93 was extensively analyzed through molecular docking, followed by MD simulations, and molecular interactions were compared with SARS-CoV-2. The relative binding poses of Z93 fitted well in the binding site of both proteases and showed consensus π-π stacking and H-bond interactions with histidine and aspartate/asparagine residues of the catalytic triad. These results led us to speculate that compound Z93 might be the first potential chemical lead against SARS-CoV-2 PLpro, which warrants in-vitro evaluations.