Identification of SARS-CoV-2 surface therapeutic targets and drugs using molecular modeling methods for inhibition of the virus entry

Although COVID-19 emerged as a major concern to public health around the world, no licensed medication has been found as of yet to efficiently stop the virus spread and treat the infection. The SARS-CoV-2 entry into the host cell is driven by the direct interaction of the S1 domain with the ACE-2 receptor followed by conformational changes in the S2 domain, as a result of which fusion peptide is inserted into the target cell membrane, and the fusion process is mediated by the specific interactions between the heptad repeats 1 and 2 (HR1 and HR2) that form the six-helical bundle. Since blocking this interaction between HRs stops virus fusion and prevents its subsequent replication, the HRs inhibitors can be used as anti-COVID drugs. The initial drug selection is based on existing molecular databases to screen for molecules that may have a therapeutic effect on coronavirus. Based on these premises, we chose two approved drugs to investigate their interactions with the HRs (based on docking methods). To this end, molecular dynamics simulations and molecular docking were carried out to investigate the changes in the structure of the SARS-CoV-2 spike protein. Our results revealed, cefpiramide has the highest affinity to S protein, thereby revealing its potential to become an anti-COVID-19 clinical medicine. Therefore, this study offers new ways to re-use existing drugs to combat SARS-CoV-2 infection

Molecular Epizootiology of Rodent Leishmaniasis in a Hyperendemic Area of Iran

"nBackground: Zoonotic cutaneous leishmaniasis (ZCL) is an expanding disease and public health problem in Iran. In the current study, natural Leishmania infection rate and seasonal fluctuation of the infection in Rhombomys opimus population of a hyperendemic focus of ZCL in Iran was investigated."nMethods:  The study was conducted from October 2006 to October 2008 in Esfahan Province, central part of Iran. An extensive sampling of rodents using Sherman traps was done in different seasons. Nested PCR assay was used for detection and identification of Leishmania species and the results were confirmed using PCR-RFLP."nResults: Leishmania infection rate was 58.6% (34 of 58) using nested PCR. 44.8% of the gerbils were infected only with L. turanica and 1.7% with L. gerbilli alone. A mixed natural infection with L. major and L. turanica was seen in 12.1% of the rodents. L. major infection alone was not seen in R. opimus population in the study area. The highest and lowest Leishmania infection rates were observed in fall and spring respectively. L. turanica infection was observed throughout the year whereas mixed infections with L. major and L. turanica was not seen in spring."nConclusion: It is concluded that in the study area, L. major, L. gerbilli and L. turanica circulate in the population of R. opimus. Leishmania major infection usually accompanied by L. turanica in naturally infected gerbils with the highest rate in fall.  It is recommended that the role of L. turanica in the epidemiology and transmission of ZCL be revisited

Karyosystematic and morphometric characterization of the rodents as reservoir hosts of zoonotic cutaneous leishmaniasis in an endemic focus of Isfahan Province, Iran

Background & objectives: Rodents belonging to Gerbillinae subfamily are the main reservoir hosts of zoonotic cutaneous leishmaniasis (ZCL) in Iran. Regarding the important role of these rodents in the maintenance of Leishmania major in the nature, their identification with morphometric, cytogenetic and molecular methods seems to be essential. The karyotype study of these species, captured from a new focus of zoonotic cutaneous leishmaniasis located in the south of Isfahan Province was carried out in 2007.Methods: Twenty specimens containing seventeen Meriones persicus and three Nesokia indica were captured from Mobarakeh rural district south of Isfahan. Giemsa-stained karyotypes of these two species were prepared from bone marrow chromosome preparations. Systematic important characters of the body and cranium (incisors, molars, occipitonasal, condylobasal, zygomatic, tympanic bullae, etc.) of these rodents were studied. Cranium size was measured using a Vernier calipers.Results: Specimens of M. persicus and N. indica had 2n = 42. The karyotype study of these species included metacentric, sub-metacentric and acrocentric chromosomes. Morphological studies were completely matched with the reported characters of these species and further confirmed the diagnoses. Interpretation & conclusion: Based on the results of this study, M. persicus and N. indica are two completely differentiated rodents species that were collected from a new focus and they can also be differentiated morphologically

Monitoring of laboratory reared of Phlebotomus papatasi (Diptera: Psychodidae), main vector of zoonotic cutaneous leishmaniasis to different imagicides in hyper endemic areas, Isfahan Province, Iran

Background: In domestic and per domestic area,insecticides such as DDT, malathion, fenitrothion, propoxur and, more recently, synthetic pyrethroids such as deltamethrin and lambda-cyhalothrin, have been successfully used to control sand flies in many countries. The present study reports the results of time-mortality bioassay to DDT 4, lambda-cyhalothrin 0.05, permethrin 0.75, cyfluthrin 0.15 and deltamethrin 0.05 in recently colonized Phlebotomus papatasi populations in Iran. Methods: The insecticide susceptibility status of P. papatasi laboratory population was assessed during 2016�2017, following the standard WHO technique for mosquito (WHO, 2013) based on diagnostic dose. Sand flies collected from rural area of Badrood (Matin Abad), Natanz County, Esfahan Province, using aspirator. Results: Susceptibility test to DDT and pyrethroids was assessed on 3534 laboratory-reared P. papatasi (1746 females and 1788 males). The LT50 and LT90 values were measured using probit analysis and regression lines. The test results against males of P. papatasi revealed that LT50 values to DDT 4, Permethrin 0.75, Deltamethrin 0.05, Cyfluthrin 0.15 and Lambdacyhalothrin 0.05 were 439.28, 108.90, 97.75, 5.00 and 57.84 seconds. The figures for females were 641.62, 136.15, 146.44, 8.71 and 72.69 seconds, respectively. Conclusion: According to presented results, the reared population of sand flies collected from a hyper-endemic region of Esfahan Province is still susceptible to prethroids and Resistance candidate to DDT 4. © 2020 Tehran University of Medical Sciences. All rights reserved