Chikungunya virus inhibition by synthetic coumarin-guanosine conjugates
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Authors: Hwu, Jih Ru; Huang, Wen-Chieh; Lin, Shu-Yu; Tan, Kui-Thong; Hu, Yu-Chen; Shieh, Fa-Kuen; Bachurin, Sergey O.; Ustyugov, Alexey; Tsay, Shwu-Chen
Since its discovery in Tanganyika, Africa in 1952, chikungunya virus (CHIKV) outbreaks have occurred in Africa, Asia, Europe, and America. Till now chikungunya fever has spread in nearly 40 countries. Because of lack of effective vaccines and antiviral drugs to intervene this disease, 21 new conjugated compounds were designed and synthesized by coupling of 6,8-dithioguanosine at its C-6 position with 3-(chloromethyl)coumarins bearing an F, Cl, Br, Me, or -OMe substituent through the -SCH2- joint. Meanwhile, an organic "dummy" ligand (e.g., methyl, benzyl, and naphthylmethyl) or a coumarinyl moiety was attached at the C-8 position. By high through-put screening, three of these new conjugates were found to inhibit CHIKV in Vero cells with significant potency (EC50 = 9.9-13.9 mu M) and showed low toxicity (CC50 = 96.5-212 mu M). The selectivity index values were 9.37-21.7. Their structure-activity relationship was deduced, which indicates that the coumarin moiety is essential and the presence of a -OMe group enhances the antiviral activity. (C) 2019 Elsevier Masson SAS. All rights reserved.
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.