High Genetic Diversity of Human Rhinovirus among Pilgrims with Acute Respiratory Tract Infections during 2019 Hajj Pilgrimage Season

OBJECTIVES: Acute Respiratory tract infections (ARI) due to Human Rhinoviruses (HRV) are common in pilgrims during the annual Hajj pilgrimage. The objective of this study was to investigate the genetic diversity of HRV among pilgrims with respiratory symptoms during Hajj 2019. METHODS: HRV infection was detected using multiplex real time RT-PCR. Cycle sequencing was performed on positive samples and the sequences were subjected to phylogenetic analysis. RESULTS: 19 HRV-positive respiratory samples were sequenced. All three serotypes of HRV were identified: HRV-A (13; [68.42%)) was more common than HRV-B (2; [10.53%]), and HRV-C (4; [21.05%]). HRV-A species were found to be of genotypes A101, A21, A30, A57, A23, A60 and A11. HRV-B species belonged to genotypes B4 and B84, and HRV-C species were of genotypes C15, C3 and C56. CONCLUSIONS: Sequencing studies of respiratory tract viruses in pilgrims are important. We provide preliminary evidence of high diversity of HRV genotypes circulating in pilgrims in a restricted area during Hajj. This requires further clinical and sequencing studies of viral pathogens in larger consorts of overseas and local pilgrims

Kaumoebavirus, a New Virus That Clusters with Faustoviruses and Asfarviridae

In this study, we report the isolation of a new giant virus found in sewage water from the southern area of Jeddah (Saudi Arabia), with morphological and genomic resemblance to Faustoviruses. This new giant virus, named Kaumoebavirus, was obtained from co-culture with Vermamoeba vermiformis, an amoeboid protozoa considered to be of special interest to human health and the environment. This new virus has ~250 nm icosahedral capsids and a 350,731 bp DNA genome length. The genome of Kaumoebavirus has a coding density of 86%, corresponding to 465 genes. Most of these genes (59%) are closely related to genes from members of the proposed order Megavirales, and the best matches to its proteins with other members of the Megavirales are Faustoviruses (43%) and Asfarviruses (23%). Unsurprisingly, phylogenetic reconstruction places Kaumoebavirus as a distant relative of Faustoviruses and Asfarviruses

Identification of Antiviral Compounds against Monkeypox Virus Profilin-like Protein A42R from <i>Plantago lanceolata</i>

Infections caused by the monkeypox virus (MPXV) have continued to be transmitted significantly in recent years. However, understanding the transmission mechanism, risk factors, and consequences of infection are still limited. Structure-based drug design for MPXV is at an early stage due to the availability of protein structures that have been determined experimentally. However, the structure of the A42R profilin-like protein of MPXV has been solved and submitted to the structure database. This study illustrated an in silico structure-based approach to identify the potential hit compound against A42R of MPXV. Here, 65 Plantago lanceolata compounds were computationally screened against A42R of MPXV. Virtual screening identified top five hits (i) Luteolin 7,3′-Diglucuronide (PubChem ID: 44258091), (ii) Luteolin 7-Glucuronide-3′-Glucoside (PubChem ID: 44258090), (iii) Plantagoside (PubChem ID: 174157), (iv) Narcissoside (PubChem ID: 5481663), and (v) (AlphaE,8S,9R)-N-(3,4-Dihydroxyphenethyl)-8-[(3,4-Dihydroxyphenethyl)Carbamoyl]-9-(1,3-Benzodioxole-5-Yl)-3aalpha,7aalpha-Ethano-1,3-Benzodioxole-5-Acrylamide (PubChem ID: 101131595), with binding energy <−9.0 kcal/mol that was further validated by re-docking and molecular dynamic (MD) simulation. Interaction analysis of re-docked poses confirmed the binding of these top hits to the A42R protein as reported in the reference compound, including active residues ARG114, ARG115, and ARG119. Further, MD simulation and post-simulation analysis support Plantagoside and Narcissoside for substantial stability in the binding pocket of viral protein contributed by hydrogen and hydrophobic interactions. The compounds can be considered for further optimisation and in vitro experimental validation for anti-monkeypox drug development

Fig 7 -

Root mean square deviation (RMSD) plots for (a) Mpro-CHEMBL1940602 (b) Mpro-CHEMBL2036486 (c) Mpro-CHEMBL3628485 (d) Mpro-CHEMBL200972 (e) Mpro-CHEMBL2036488, and (fCH) Mpro-X77 (control), calculated over the period of 100 ns MD simulation.</p

Fig 9 -

Principal component cluster analysis along first three PCs for (a1-a4) CHEMBL1940602, (b1-b4) CHEMBL2036486, (c1-c4) CHEMBL3628485, (d1-d4) CHEMBL200972, (e1-e4) CHEMBL2036488 and (f1-f4) X77 (control). The spread of dots represents the degree of conformational change while the colour code represents the time steps (blue: initial, white: intermediate and red: final).</p

Fig 6 -

Dynamic flexibility depiction using first and last pose obtained from MD simulation for (a) Mpro-CHEMBL1940602 (b) Mpro-CHEMBL2036486 (c) Mpro-CHEMBL3628485 (d) Mpro-CHEMBL200972 (e) Mpro-CHEMBL2036488, and (f) Mpro-X77 (control).</p

Native ligand (X77)-protein (PDB structure 6W63) 2D interactions plot: Representation of intermolecular interaction between native ligand and the active site amino acid residue of the target protein.

Native ligand (X77)-protein (PDB structure 6W63) 2D interactions plot: Representation of intermolecular interaction between native ligand and the active site amino acid residue of the target protein.</p

Intermolecular interactions noted for the screened compounds with the SARS-CoV-2 M^pro within 4 Å around the docked ligand in the respective binding pockets.

Intermolecular interactions noted for the screened compounds with the SARS-CoV-2 Mpro within 4 Å around the docked ligand in the respective binding pockets.</p

Fig 8 -

2D interaction diagram of protein-ligand interactions maps for (a) Mpro-CHEMBL1940602 (b) Mpro-CHEMBL2036486 (c) Mpro-CHEMBL3628485 (d) Mpro-CHEMBL200972 (e) Mpro-CHEMBL2036488, and (f) Mpro-X77 (control), over the 100 ns MD simulation.</p

Crystal structure of M^pro (PDB ID: 6W63) representing Domain I, II and III with the co-crystalized ligand (PDB code: X77).

Crystal structure of Mpro (PDB ID: 6W63) representing Domain I, II and III with the co-crystalized ligand (PDB code: X77).</p