BACKGROUND: In the last couple of years, viral infections have been leading the globe, considered one of the most widespread and extremely damaging health problems and one of the leading causes of mortality in the modern period. Although several viral infections are discovered, such as SARS CoV-2, Langya Henipavirus, there have only been a limited number of discoveries of possible antiviral drug, and vaccine that have even received authorization for the protection of human health. Recently, another virial infection is infecting worldwide (Monkeypox, and Smallpox), which concerns pharmacists, biochemists, doctors, and healthcare providers about another epidemic. Also, currently no specific treatment is available against Monkeypox. This research gap encouraged us to develop a new molecule to fight against monkeypox and smallpox disease. So, firstly, fifty different curcumin derivatives were collected from natural sources, which are available in the PubChem database, to determine antiviral capabilities against Monkeypox and Smallpox. MATERIAL AND METHOD: Preliminarily, the molecular docking experiment of fifty different curcumin derivatives were conducted, and the majority of the substances produced the expected binding affinities. Then, twelve curcumin derivatives were picked up for further analysis based on the maximum docking score. After that, the density functional theory (DFT) was used to determine chemical characterizations such as the highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO), softness, and hardness, etc. RESULTS: The mentioned derivatives demonstrated docking scores greater than 6.80 kcal/mol, and the most significant binding affinity was at -8.90 kcal/mol, even though 12 molecules had higher binding scores (-8.00 kcal/mol to -8.9 kcal/mol), and better than the standard medications. The molecular dynamic simulation is described by root mean square deviation (RMSD) and root-mean-square fluctuation (RMSF), demonstrating that all the compounds might be stable in the physiological system. CONCLUSION: In conclusion, each derivative of curcumin has outstanding absorption, distribution, metabolism, excretion, and toxicity (ADMET) characteristics. Hence, we recommended the aforementioned curcumin derivatives as potential antiviral agents for the treatment of Monkeypox and Smallpox virus, and more in vivo investigations are warranted to substantiate our findings.
- MeSH
- Antiviral Agents pharmacology MeSH
- COVID-19 * MeSH
- Curcumin * pharmacology MeSH
- Humans MeSH
- Drug Discovery MeSH
- Mpox, Monkeypox * MeSH
- Smallpox * drug therapy MeSH
- Drug Design MeSH
- Molecular Dynamics Simulation MeSH
- Molecular Docking Simulation MeSH
- Variola virus * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Acknowledging the importance of studies toward the development of measures against terrorism and bioterrorism, this study aims to contribute to the design of new prototypes of potential drugs against smallpox. Based on a former study, nine synthetic feasible prototypes of selective inhibitors for thymidylate kinase from Variola virus (VarTMPK) were designed and submitted to molecular docking, molecular dynamics simulations and binding energy calculations. The compounds are simplifications of two more complex scaffolds, with a guanine connected to an amide or alcohol through a spacer containing ether and/or amide groups, formerly suggested as promising for the design of selective inhibitors of VarTMPK. Our study showed that, despite the structural simplifications, the compounds presented effective energy values in interactions with VarTMPK and HssTMPK and that the guanine could be replaced by a simpler imidazole ring linked to a -NH2 group, without compromising the affinity for VarTMPK. It was also observed that a positive charge in the imidazole ring is important for the selectivity toward VarTMPK and that an amide group in the spacer does not contribute to selectivity. Finally, prototype 3 was pointed as the most promising to be synthesized and experimentally evaluated. Communicated by Ramaswamy H. Sarma.
- MeSH
- Enzyme Inhibitors chemistry pharmacology therapeutic use MeSH
- Humans MeSH
- Ligands MeSH
- Nucleoside-Phosphate Kinase antagonists & inhibitors chemistry MeSH
- Smallpox drug therapy MeSH
- Drug Design * MeSH
- Molecular Dynamics Simulation MeSH
- Molecular Docking Simulation MeSH
- Thermodynamics MeSH
- Variola virus enzymology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
The complete genome sequences of two strains of variola virus (VARV) sampled from human smallpox specimens present in the Czech National Museum, Prague, were recently determined, with one of the sequences estimated to date to the mid-19th century. Using molecular clock methods, the authors of this study go on to infer that the currently available strains of VARV share an older common ancestor, at around 1350 AD, than some recent estimates based on other archival human samples. Herein, we show that the two Czech strains exhibit anomalous branch lengths given their proposed age, and by assuming a constant rate of evolutionary change across the rest of the VARV phylogeny estimate that their true age in fact lies between 1918 and 1937. We therefore suggest that the age of the common ancestor of currently available VARV genomes most likely dates to late 16th and early 17th centuries and not ~1350 AD.
- MeSH
- Phylogeny MeSH
- Genome, Viral MeSH
- Humans MeSH
- Evolution, Molecular MeSH
- Museums MeSH
- Smallpox * MeSH
- Variola virus genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Comment MeSH
- Geographicals
- Czech Republic MeSH
Although smallpox has been known for centuries, the oldest available variola virus strains were isolated in the early 1940s. At that time, large regions of the world were already smallpox-free. Therefore, genetic information of these strains can represent only the very last fraction of a long evolutionary process. Based on the genomes of 48 strains, two clades are differentiated: Clade 1 includes variants of variola major, and clade 2 includes West African and variola minor (Alastrim) strains. Recently, the genome of an almost 400-year-old Lithuanian mummy was determined, which fell basal to all currently sequenced strains of variola virus on phylogenetic trees. Here, we determined two complete variola virus genomes from human tissues kept in a museum in Prague dating back 60 and 160 years, respectively. Moreover, mass spectrometry-based proteomic, chemical, and microscopic examinations were performed. The 60-year-old specimen was most likely an importation from India, a country with endemic smallpox at that time. The genome of the 160-year-old specimen is related to clade 2 West African and variola minor strains. This sequence likely represents a new endemic European variant of variola virus circulating in the midst of the 19th century in Europe.
- MeSH
- History, 19th Century MeSH
- History, 20th Century MeSH
- DNA, Viral genetics MeSH
- Phylogeny MeSH
- Genome, Viral * MeSH
- Humans MeSH
- Evolution, Molecular MeSH
- Museums * MeSH
- Polymerase Chain Reaction MeSH
- Smallpox epidemiology history virology MeSH
- Proteomics MeSH
- Variola virus classification genetics MeSH
- High-Throughput Nucleotide Sequencing MeSH
- Check Tag
- History, 19th Century MeSH
- History, 20th Century MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
- Historical Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic MeSH
- Europe MeSH
- India epidemiology MeSH
- MeSH
- Bacillus anthracis MeSH
- Biological Warfare Agents MeSH
- Burkholderia mallei MeSH
- Clostridium botulinum MeSH
- Coronavirus MeSH
- Coxiella burnetii MeSH
- Decontamination MeSH
- Francisella tularensis MeSH
- Hemorrhagic Fevers, Viral MeSH
- Disasters MeSH
- Infection Control MeSH
- Communicable Disease Control MeSH
- Containment of Biohazards MeSH
- Personal Protective Equipment MeSH
- Ricin MeSH
- Rickettsia prowazekii MeSH
- Saxitoxin MeSH
- Biohazard Release MeSH
- Emergency Medical Services MeSH
- Vibrio cholerae MeSH
- Influenza A Virus, H1N1 Subtype MeSH
- Variola virus MeSH
- Environmental Exposure MeSH
- Yersinia pestis MeSH
- MeSH
- Allergy and Immunology * history trends MeSH
- Child MeSH
- Epidemics prevention & control MeSH
- Disease Attributes MeSH
- Humans MeSH
- Measles * diagnosis prevention & control virology MeSH
- Statistics as Topic MeSH
- Vaccines administration & dosage adverse effects therapeutic use MeSH
- Variola virus * isolation & purification MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Geographicals
- United States MeSH
- MeSH
- Acyclovir administration & dosage therapeutic use MeSH
- Alphapapillomavirus pathogenicity MeSH
- Antiviral Agents administration & dosage therapeutic use MeSH
- Warts etiology physiopathology therapy MeSH
- Exanthema Subitum etiology physiopathology MeSH
- Herpes Zoster etiology drug therapy physiopathology MeSH
- Herpesviridae Infections etiology drug therapy physiopathology MeSH
- Condylomata Acuminata etiology physiopathology therapy MeSH
- Humans MeSH
- Herpesvirus 6, Human pathogenicity MeSH
- Molluscum Contagiosum etiology physiopathology therapy MeSH
- Chickenpox etiology drug therapy physiopathology MeSH
- Smallpox etiology physiopathology MeSH
- Simplexvirus pathogenicity MeSH
- Skin Diseases, Viral * etiology physiopathology therapy MeSH
- Molluscum contagiosum virus pathogenicity MeSH
- Herpesvirus 3, Human pathogenicity MeSH
- Variola virus pathogenicity MeSH
- Check Tag
- Humans MeSH
Před 214 lety provedl anglický venkovský lékař Edward Jenner první a bezpečné očkování vakcinálním virem a stál tak na počátku unikátního procesu, který vyvrcholil právě před 30 lety eradikací neštovičného viru a definitivním zlikvidováním této choroby.
- MeSH
- Biological Warfare Agents MeSH
- Humans MeSH
- Smallpox epidemiology prevention & control transmission MeSH
- Healthy People Programs utilization MeSH
- World Health Organization MeSH
- Smallpox Vaccine history therapeutic use MeSH
- Variola virus pathogenicity MeSH
- Weapons of Mass Destruction MeSH
- Check Tag
- Humans MeSH
- Publication type
- Interview MeSH
