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.

Background/Objectives: Monkeypox is a re-emerging viral disease with features of infectiously transmitted zoonoses. It is now considered a public health priority because of its rising incidence and transmission from person to person. Monkeypox virus (MPXV) VP39 protein is identified as an essential protein for replication of the virus, and therefore, it is a potential target for antiviral drugs. Methods: This work analyzes the binding affinities and the differential conformational stability of three target compounds and one control compound with the VP39 protein through multiple computational methods. Results: The re-docking analysis revealed that the compounds had high binding affinities towards the target protein; among these compounds, compounds 1 and 2 showed the highest binding energies in the virtual screening, and thus, these were considered as the most active inhibitor candidates. Intermolecular interaction analysis revealed distinct binding mechanisms. While compound 1 had very strong hydrogen bonds and hydrophobic interactions, compound 2 had numerous water-mediated interactions, and compound 3 had only ionic and hydrophobic contacts. In molecular dynamic simulations, compounds 1 and 2 showed that the protein–ligand complexes had a stable conformation, with protein RMSD values around 2 Å for both compounds. In contrast, compound 3 was slightly flexible, and the control compound was more flexible. MM/GBSA analysis again supported these results, which gave the binding free energies that were also supportive for these compounds. Conclusions: Notably, all the selected compounds, especially compounds 1 and 2, demonstrate high binding affinity. Therefore, these compounds can be further tested as antiviral agents against monkeypox treatment.

Coronavirus disease-19 (COVID-19) pandemic, caused by the novel SARS-CoV-2 virus, continues to be a global threat. The number of cases and deaths will remain escalating due to the lack of effective therapeutic agents. Several studies have established the importance of the viral main protease (M^pro) in the replication of SARS-CoV-2 which makes it an attractive target for antiviral drug development, including pharmaceutical repurposing and other medicinal chemistry approaches. Identification of natural products with considerable inhibitory potential against SARS-CoV-2 could be beneficial as a rapid and potent alternative with drug-likeness by comparison to de novo antiviral drug discovery approaches. Thereof, we carried out the structure-based screening of natural products from Echinacea-angustifolia, commonly used to prevent cold and other microbial respiratory infections, targeting SARS-CoV-2 M^pro. Four natural products namely, Echinacoside, Quercetagetin 7-glucoside, Levan N, Inulin from chicory, and 1,3-Dicaffeoylquinic acid, revealed significant docking energy (>−10 kcal/mol) in the SARS-CoV-2 M^pro catalytic pocket via substantial intermolecular contacts formation against co-crystallized ligand (<−4 kcal/mol). Furthermore, the docked poses of SARS-CoV-2 M^pro with selected natural products showed conformational stability through molecular dynamics. Exploring the end-point net binding energy exhibited substantial contribution of Coulomb and van der Waals interactions to the stability of respective docked conformations. These results advocated the natural products from Echinacea angustifolia for further experimental studies with an elevated probability to discover the potent SARS-CoV-2 M^pro antagonist with higher affinity and drug-likeness.

The Ebola virus and its close relative, the Marburg virus, both belong to the family Filoviridae and are highly hazardous and contagious viruses. With a mortality rate ranging from 23% to 90%, depending on the specific outbreak, the development of effective antiviral interventions is crucial for reducing fatalities and mitigating the impact of Marburg virus outbreaks. In this investigation, a virtual screening approach was employed to evaluate 2042 natural compounds for their potential interactions with the VP35 protein of the Marburg virus. Average and worst binding energies were calculated for all 20 poses, and compounds that exhibited binding energies <−6 kcal/mol in both criteria were selected for further analysis. Based on binding energies, only six compounds (Estradiol benzoate, INVEGA (paliperidone), Isosilybin, Protopanaxadiol, Permethrin, and Bufalin) were selected for subsequent investigations, focusing on interaction analysis. Among these selected compounds, Estradiol benzoate, INVEGA (paliperidone), and Isosilybin showed strong hydrogen bonds, while the others did not. In this study, the compounds Myricetin, Isosilybin, and Estradiol benzoate were subjected to a molecular dynamics (MD) simulation and free binding energy calculation using MM/GBSA analysis. The reference component Myricetin served as a control. Estradiol benzoate exhibited the most stable and consistent root-mean-square deviation (RMSD) values, whereas Isosilybin showed significant fluctuations in RMSD. The compound Estradiol benzoate exhibited the lowest ΔG binding free energy (−22.89 kcal/mol), surpassing the control compound’s binding energy (−9.29 kcal/mol). Overall, this investigation suggested that Estradiol benzoate possesses favorable binding free energies, indicating a potential inhibitory mechanism against the VP35 protein of the Marburg virus. The study proposes that these natural compounds could serve as a therapeutic option for preventing Marburg virus infection. However, experimental validation is required to further corroborate these findings.

Since the recent discovery of Samba virus, the first representative of the family Mimiviridae from Brazil, prospecting for mimiviruses has been conducted in different environmental conditions in Brazil. Recently, we isolated using Acanthamoeba sp. three new mimiviruses, all of lineage A of amoebal mimiviruses: Kroon virus from urban lake water; Amazonia virus from the Brazilian Amazon river; and Oyster virus from farmed oysters. The aims of this work were to sequence and analyze the genome of these new Brazilian mimiviruses (mimi-BR) and update the analysis of the Samba virus genome. The genomes of Samba virus, Amazonia virus and Oyster virus were 97%–99% similar, whereas Kroon virus had a low similarity (90%–91%) with other mimi-BR. A total of 3877 proteins encoded by mimi-BR were grouped into 974 orthologous clusters. In addition, we identified three new ORFans in the Kroon virus genome. Additional work is needed to expand our knowledge of the diversity of mimiviruses from Brazil, including if and why among amoebal mimiviruses those of lineage A predominate in the Brazilian environment.