EFFECTS OF DRUGS ON SPIKE GLYCOPROTEIN OF SARS-COV 2 IN CONTROL OF COVID-2019

Dowluru SVGK Kaladhar Department of Microbiology and Bioinformatics, UTD, Atal Bihari Vajpayee University, Bilaspur (Chhattisgarh), India. ...................................................................................................................... Manuscript Info Abstract ......................... ........................................................................ Manuscript History Received: 20 January 2020 Final Accepted: 22 February 2020 Published: March 2020


…………………………………………………………………………………………………….... Introduction:-
New infectious diseases from several microbes emerged from past 50,000-100,000 years till modern humans (Kidgell et al., 2002;Stringer, 1990). Several viral diseases like smallpox, mumps, rubella, polio, influenza, herpes viruses, poliovirus, rabies, yellow fever, dengue fever, HIV and Severe Acute Respiratory Syndrome (SARS) are effected to humans from about 10,000 years ago (Grabenstein and Nevin,2006). Some of the diseases are epidemics or pandemic of viral diseases effected on large number of people worldwide. The rare epidemics of viral diseases that are originating in animals will be short-lived as the emerged viruses were not fully adapted to humans. Measles was so common in children but COVID-19 is most common in people of all ages that destroys respiratory system. Some infectious diseases may play a major role in the development of Parkinson's disease (Vlajinac et al., 2003).
In recent decades several antiviral drugs and anti-inflammatory compounds (Chattopadhyay et al., 2009) have been developed to specifically target viruses for quicker recovery although vaccines are still the most powerful weapon against viruses. Ayurveda is perhaps originated 5,000 years ago in India for the treatment of diseases. Treatment of new emerging viral diseases is challenges for medical scientists from ancient times. Neem (Azadirachta indica) is a commonly grown medicinal herb that helps in the recovery from chicken pox. The Neem is brewed together with chrysanthemum used to drink as herbal tea for development of immune system and keeping away of acne, chicken pox and measles. Turmeric mixed with boiled milk or water is used to be taken for the treatment of intestinal disorders, viral fevers, cold and sore throats. An ancient Ayurvedic text Charaka Samhita provided information on illness from smallpox, with a recommended treatment of a poultice of neem leaves and turmeric (Nene, 2007).

Genome retrieval and structure prediction of spike Glycoprotein from SARS-CoV-2:
The SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) complete genome sequence has been retrieved from the NCBI database (Accession number NC_045512.2) that is an isolate from Wuhan-Hu-1 of China. The gene prediction (Kaladhar and Krishna, 2011) for SARS-CoV-2 complete genome was predicted using FGENESV0. The gene identification for the protein sequences has been submitted to BLASTp and selected spike glycoprotein. The protein sequence was submitted to swissmodel and 3D model ( Figure 1) was obtained for docking studies.

Properties of computer:
The system properties in the present work are as follows: Processor: Pentium (R) Dual-core CPU E5200 with 2.50 GHz, 2GB RAM and 32 bit Operating system.

Docking studies:
The modeled structure of spike glycoprotein of SARS-CoV-2 is selected as receptor in the present study. The docking studies of spike glycoprotein with selected ligands are conducted using iGEMDOCK v2.1 software.

Results:-
The SARS-CoV-2 genome sequence of NC_045512.2 related to severe acute respiratory syndrome coronavirus 2 isolate Wuhan-Hu-1, complete genome has been retrieved from NCBI. The complete genome has 29903 bp, ss-RNA with linear structure. The spike glycoprotein of SARS-CoV-2 is 3849 bp length that is present from 21536 to 25384 location, as per the prediction from FGENESV0 server. The sequence is related to SARS genome based on the identification method used by BLASTp.
The structure of the identified SARS-CoV-2 was shown in The tiny molecular key on SARS-CoV-2 that gives the virus entry into the cell is called a spike glycoprotein, or Sglycoprotein. Hence spike surface glycoprotein is the main protein to be concentrated for understanding effects with anti-viral drugs and drugs. The lower the value of Ki, the more will be favorable is the binding. Hence, the docking studies with lower energies show better activity of ligands with receptor (Table 1). The docked poses of Curcumin (Enol form) and Ombitasvir with SARS-CoV-2 respectively has been shown in Figure 4.

Discussion:-
Coronaviruses appear as pleiomorphic, 120-160nm in diameter, roughly spherical, with a characteristic fringe of large (ca. 20nm), petal-shaped surface projections comprised of trimers of the spike (S) glycoprotein. The spike (S) glycoprotein of SARS-CoV-2 is responsible for receptor binding and a major antigenic determinant that is capable of inducing protective immunity. Receptor-binding domain (RBD) of S glycoprotein is an important immunogenic site in patients is a critical neutralization determinant of SARS-CoV-2 during viral infection and immunization (He et al., 2005).
Plants play important role in control of several viral diseases. The selected ligands in the present work and the availability from plant sources were shown in Table 2. The total number of cases is increasing and may have millions of confirmed cases/ deaths by the end of year 2020. The coronavirus COVID-19 was affected many countries and territories around the world and international conveyances. The experimentation has shown that turmeric powder, tea and sun light can treat COVID-19 in natural way.

Conclusion:-
Large number of viruses has been emerged for the ancient times from China. There is a need to control these new emerging viruses to several counties before spread. The development of immune system through natural sources, distance maintenance and isolation of people (Fast pandemic to slow pandemic), avoiding exchange of materials like plastics, utensils, etc, washing hands with soap solution, use of antiviral drugs, medicinal compounds like turmeric powder, tea, vitamin D (sitting in morning sun light) and vaccines are better methods to control COVID-19.