In-silico prediction of novel drug-target complex of nsp3 of CHIKV through molecular dynamic simulation
Authors: Kumar, Durgesh; Meena, Mahendra Kumar; Kumari, Kamlesh; Patel, Rajan; Jayaraj, Abhilash; Singh, Prashant
Literature reported that nsp3 of CHIKV is an important target for the designing of drug as it involves in the replication, survival etc. Herein, about eighteen million molecules available in the ZINC database are filtered against nsp3 using RASPD. Top five hit drug molecules were then taken from the total screened molecules (6988) from ZINC database. Then, a one pot-three components reaction is designed to get the pyrazolophthalazine and its formation was studied using DFT method. Authors created a library of 200 compounds using the product obtained in the reaction and filtered against nsp3 of CHIKV based on docking using iGEMDOCK, a computational tool. Authors have studied the best molecules after applying the the Lipinski's rule of five and bioactive score. Further, the authors took the best compound i.e. CMPD178 and performed the MD simulations and tdMD simulations with nsp3 protease using AMBER18. MD trajectories were studied to collect the information about the nsp3 of CHIKV with and without screened compound and then, MM-GBSA calculations were performed to calculate change in binding free energies for the formation of complex. The aim of the work is to find the potential candidate as promising inhibitor against nsp3 of CHIKV.
Frequency, Awareness, and Symptoms of Chikungunya Among Patients in a Tertiary Care Hospital of Karachi: A Cross-Sectional Study
Authors: Mehdi, Zoha; Shahbaz, Hareem; Owais, Aatika; Hasan, Syeda Ushna; Nasr, Ifrah; Jahangir, Ahmed; Zubair, Nashmia; Khaliq, Syed Abdullah Abdul; Khalid, Maria; Shahbaz, Sana; Qureshi, Momina; Hasan, Raazia; Fasih, Muhammad; Khalid, Adeel; Hasan, Dania; Nigar, Soofia
Background Chikungunya fever (CHIKF) is an infectious illness spread by the bite of mosquitoes and caused by an arbovirus known as Chikungunya virus (CHIKV). This disease has become an epidemic in Karachi and various other cities of Pakistan, affecting a large population, especially those from poor, socioeconomically underdeveloped areas. It is proving to be a severe and alarming cause of debility due to its prolonged detrimental effects on the joints. A significant number of cases are reported daily in different hospitals of Karachi, with Civil Hospital being one of the major tertiary care hospitals. The aim of this study is to determine the frequency and symptoms of chikungunya as well as to assess the participants' awareness about the spread and preventive measures of this disease. Methods This is a cross-sectional study that was carried out in Civil Hospital Karachi by approaching patients in the out-patient department (OPD) and the emergency department with complaints of fever and joint pain. All the data was collected via a pre-coded questionnaire during May-June 2017 by taking prior informed verbal consent and were analyzed through Statistical Package for the Social Sciences (SPSS) version 22 software. Results The age group most affected by this disease was the 21-30 years range, which represented almost a quarter of the cases (n= 83, 32.17%). Majority of the respondents (n= 214, 82.95%) had heard of the disease, mainly due to their own prior experience with it (n= 100, 38.76%). Lethargy (n= 219, 84.88%), difficulty in walking (n= 213, 82.56%), and headache (n= 209, 81.01%) were the major symptoms reported apart from fever (n= 258, 100.00%) and arthralgia (n= 258, 100.00%). Conclusion CHIKF is proving to be a great threat to people as it impairs their quality of life to a great extent. The recent outbreak of chikungunya has victimized a considerable population of Karachi. This study mainly assessed the severity of the disease and its symptoms as well as the lack of awareness among patients. Proper and effective preventive measures can further help to eradicate this disease on a large scale and prevent future epidemics.