George Walton Comprehensive High School Marietta, Georgia, United States
Abhishek Kona (George Walton Comprehensive High School)| Abhinav Kona (George Walton Comprehensive High School)| Sreelatha Aramgam (Emory University School of Medicine)| Kesavulu Muppuru (Sree Vidhyanikethan Engineering College)| Kameswara Badri (Morehouse School of Medicine)
Introduction - COVID19 has become one of the world’s leading problems. The severe acute respiratory syndrome coronavirus (SARS-CoV)-2 enters the human body through droplet transmission and oroanal route. The pathological manifestations of SARS-CoV-2 is mediated through key proteins involved in viral entry into the host and replication of the virus within the host. Specifically, the RNA Dependent RNA Polymerase (RdRp) employs a replicative function in multiplying and transmitting the virus, aided by other nsps, nsp7 and 8 forming functional complex; similarly, the spike protein is necessary for the virus to enter the host by binding to ACE receptors. Given the limited available treatments and urgency for the development of prophylactic agents and therapeutic drugs for the control of SARS-CoV-2 and treatment of COVID19, traditional treatment methods using natural resources are decisive. To address the pandemic, a drug targeting the function of these key proteins and protein complexes will be potentially more successful and effective. Use of medically important plants with antiviral activity including, Glycyrrhiza glabra (G glabra) and isolation of potential natural active ingredients is more beneficial and effective. Here we elucidated the potential interactions of known phytochemicals from G glabra and key SARS-CoV-2 proteins.
Methods - A molecular docking algorithm, PatchDock, was used to study the interactions between viral target proteins and phytochemicals of G. glabra. The molecular display program, Chimera was used to display the interactions between the phytochemicals of G. glabra and viral proteins.
Results - Of the 20 reported compounds (GG1 - GG20) that we used for our studies, 13 of the compounds have effectively bound to inhibit the SARS-CoV-2 proteins, nsp7/8/12 complex including RdRp and/or spike protein. Specifically, the compounds GG3 and GG4 achieved lower ACE scores than -100 binding to all three key proteins of the SARS-COV-2. Compound GG4 binds to the Spike Protein that mediate binding of SARS-COV-2 to the ACE Receptor of host cell, thereby inhibiting the entry of virus. GG4 also binds to close to the active site of nsp-complex. However, GG3 binds close to the active site of the RdRp where the thumb, finger, and palm domains meet. GG3 also binds close to the nsp7/8/12 complex in which chains 7 and 12 join together, forming a more effective complex to inhibit the viral replication. Our additional docking studies of phytochemicals of G. glabra and viral proteins will show effective binding of phytochemicals with viral proteins that inhibit either the entry and/or replication and transmission of the SARS-CoV-2.
Conclusion – In conclusion, GG3 and GG4 from Glycyrrhiza glabra have demonstrated the ability to prevent the entry and replication of SARS-COV-2 proteins by inhibiting the functions of Spike and RdRp proteins in silico.