December 2019 the new pandemic Covid-19 sweeps the world and impose unmatched challenges on modern humanity, the virus started from Wuhan China and in just a few months the virus had spread to other countries and WHO (World Health Organization) called the disease a pandemic, Covid-19 is caused by the virus SARS-CoV -2 (severe acute respiratory syndrome-Coronavirus2), the virus is largely spread through human-to-human transmission, today more than 263 million people have been infected with the virus while more than 5 million have died.
SARS-CoV-2 is closely related to other viruses of the genus Betacoronavirus such as bat coronavirus BatCoV RaTG13 (~ 96% sequence identity) and SARS-CoV (~ 80% sequence identity), Coronavirus such as SARS-CoV and SARS-CoV -2 need main protease MPro (3CLPro), MPro is interesting as there are no similar proteases in humans, and it is vital for virus survival as it has essential role in processing and replicating polyproteins of viral RNA.
ML188 is a SARS-CoV MPro inhibitor, SARS-CoV and SARS-CoV -2 have 80% sequence identity, ML188 can be used as a starting point to analyze and improve MPro inhibitors that can be used against SARS-CoV -2.
In this study with the use of UGI reaction to synthesized and modified analog to ML188 by exchanging 3-pyridialkarboxaldehyd which is one of the 4 starting material the compound with 4-pyridilkarboxaldehyd. By changing the nitrogen position in the aromatic ring, we want to see if this change can increase or decrease the compound effectiveness and if it has deferent effect on SARS-CoV2.
TLC and LC-MS are analysis method that is used to monitor the reaction and determine the purity of the reaction, column chromatography is used to purify the reaction mixture, NMR analysis both proton and carbon NMR is used to confirm the structure of our synthesized product. Result from the LCMS-Analyze showed a clear high peak with the exact mass of our Sought product but it also showed that the purification of the mixture didn’t happen fully thus we still had some impurities in the mixture. both the proton and carbon NMR results data were consistent with our compound structure. Now we need to test if this new compound can result to better inhibition in SARS-CoV2.