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1.
Curr Neuropharmacol ; 2022 Jun 27.
Article in English | MEDLINE | ID: covidwho-1910806

ABSTRACT

The vaccine development for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is primarily focused on structure of the spike (S) protein. The heavy glycosylation of S with flexible hinges at stalk shields from antibodies. The flexible nature of hinges may be one of the important factors which are responsible for binding the odorant receptor of those neurons which are responsible for the loss of smell in patients with COVID-19 infection. In this study strong and stable bond formation results from reaction between R:14: Trp and Phe at the residue, the expected outcome of this research may help in designing a novel vaccine that targets the flexible hinges of SARS-CoV-2. The difference in the conformational structure of S protein and their binding with the odorant receptor in COVID-19 are prime factor for the loss of smell and taste in patients supported by the concept of Antigen (epitope) Antibody interaction by stable formation of Hydrogen bond among odorant receptor and the S protein. The flexibility of structural proteins determines if the antibodies or other defense proteins produced are homologous participating in antigen antibody reaction thus maintaining the most neutralization sensitive epitope to produce the new vaccine strain or in isolating most effectively neutralizing human mABs. Molecular and atomic level details potentiate the design and screening of small molecules that can inhibit the fusion at entry level or at odorant receptors and potentially be used in prevention and treatment of infection particularly when formulated as nasal drops, paving a new approach for pharmacologist in treatment of COVID-19 infection.

2.
Curr Pharm Des ; 28(12): 981-992, 2022.
Article in English | MEDLINE | ID: covidwho-1760077

ABSTRACT

BACKGROUND: Corona Virus Disease-19 (COVID-19), a current worldwide pandemic is the cause of serious concern. Risk-adjusted differences in outcomes of the patients are not well characterized. Therefore, susceptibility to infection with respect to blood group, blood pressure, pulse rate, hemoglobin, age, and BMI is analyzed in this study. METHODS: Blood donors of all ages and gender, who recovered from COVID-19 infection, were selected for the study. Samples were collected from the regional laboratory and the central blood bank of Hafr al Batin, Saudi Arabia. Out of 1508 healthy blood donors, 134 had recovered from corona without any preexisting diseases. RESULTS: Major donors were male (85.1%). 28% of donors were in the age range of 26-35 years. O+(32.8%) donors were in majority. Systolic and diastolic blood pressure and pulse rate elevated significantly in the age group 46-55 (p<0.05) and 56-65 (p<0.001). Systolic blood pressure in males (134.13 ± 9.57) was significantly higher (p<0.05) than in females (129.35 ± 10.61). Donors with Rh+ had significantly higher systolic (p<0.05) and pulse rate (p<0.05) as compared to Rh-. DISCUSSION: O+ donors were found to be highly susceptible. Blood pressure, pulse rate and Hb altered with age. Males exhibited higher variation in systolic blood pressure, with the Rh+ factor playing a predominant role. Donors above 45-years of age and with a high BMI had significantly elevated blood pressure and pulse. These results are challenging or contradictory to the results of Turkish and Chinese studies where blood group A+ was more predominantly affected by the SARS-CoV-2 with the minimum infection rate in females and Rh- donors. CONCLUSION: Factors like blood group, age, physical characteristics and BMI should be taken into account before initiating any therapeutic approach to obtain the best possible outcomes with minimum adverse effects from the current drugs utilized for SARS CoV-2 treatment, especially with the age group of 45 years and above.


Subject(s)
Blood Group Antigens , COVID-19 , Adult , Blood Donors , Female , Humans , Male , Middle Aged , Pandemics , Rh-Hr Blood-Group System , SARS-CoV-2
3.
J Biomol Struct Dyn ; 39(11): 4175-4184, 2021 07.
Article in English | MEDLINE | ID: covidwho-1343548

ABSTRACT

SARS coronavirus (COVID-19) is a real health challenge of the 21st century for scientists, health workers, politicians, and all humans that has severe cause epidemic worldwide. The virus exerts its pathogenic activity through by mechanism and gains the entry via spike proteins (S) and Angiotensin-Converting Enzyme 2 (ACE2) receptor proteins on host cells. The present work is an effort for a computational target to block the residual binding protein (RBP) on spike proteins (S), Angiotensin-Converting Enzyme 2 (ACE2) receptor proteins by probiotics namely Plantaricin BN, Plantaricin JLA-9, Plantaricin W, Plantaricin D along with RNA-dependent RNA polymerase (RdRp). Docking studies were designed in order to obtain the binding energies for Plantaricin metabolites. The binding energies for Plantaricin W were -14.64, -11.1 and -12.68 for polymerase, RBD and ACE2 respectively comparatively very high with other compounds. Plantaricin W, D, and JLA-9 were able to block the residues (THR556, ALA558) surrounding the deep grove catalytic site (VAL557) of RdRp making them more therapeutically active for COVID-19. Molecular dynamics studies further strengthen stability of the complexes of plantaricin w and SARS-CoV-2 RdRp enzyme, RBD of spike protein, and human ACE2 receptor. The present study present multi-way options either by blocking RBD on S proteins or interaction of S protein with ACE2 receptor proteins or inhibiting RdRp to counter any effect of COVID-19 by Plantaricin molecules paving a way that can be useful in the treatment of COVID-19 until some better option will be available.Communicated by Ramaswamy H. Sarma.


Subject(s)
COVID-19 , Probiotics , Antiviral Agents/pharmacology , Humans , Protein Binding , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/metabolism
4.
Curr Pharm Des ; 27(9): 1202-1210, 2021.
Article in English | MEDLINE | ID: covidwho-1069678

ABSTRACT

BACKGROUND: The spike (S) glycoprotein of SARS corona virus (SARS-CoV-2) and human Angiotensin- converting enzyme 2 (ACE2), are both considered the key factors for the initiation of virus infection. The present work is an effort for computational target to block the spike proteins (S) and ACE2 receptor proteins with Macrolide antibiotics like Azithromycin, (AZM), Clarithromycin (CLAM) and Erythromycin (ERY) along with RNA-dependent RNA polymerase (RdRp). METHODS: Three-dimensional structure of the SARS-CoV-2RdRp was built by the SWISS-MODEL server, the generated structure showed 96.35% identity to the available structure of SARS-Coronavirus NSP12 (6NUR), for model validity, we utilized the SWISS-model server quality parameters and Ramachandran plots. RESULTS: These compounds were able to block the residues (Arg553, Arg555, and Ala558) surrounding the deep grove catalytic site (Val557) of RdRp and thus plays an important role in tight blocking of enzyme active site. Reference drug Remdesivir was used to compare the docking score of antibiotics with RdRp. Docking value exhibited good binding energy (-7.7 up to -8.2 kcal/mol) with RdRp, indicating their potential as a potent RdRp inhibitor. Interaction of CLAM and ERY presented low binding energy (-6.8 and -6.6) with the ACE2 receptor. At the same time, CLAM exhibited a good binding affinity of -6.4 kcal/mol, making it an excellent tool to block the attachment of spike protein to ACE2 receptors. Macrolides not only affected the attachment to ACE2 but also blocked the spike proteins further, consequently inhibiting the internalization in the host cell. Three Alkyl bonds between Arg555, Ala558, and Met542 by CLAM and two Alkyl bonds of Arg624 and Lys621 by ERY plays an important role for RdRp inactivation, that can prevent the rise of newly budded progeny virus. These macrolides interacted with the main protease protein in the pocket responsible for the dimerization and catalytic function of this protein. The interaction occurred with residue Glu166, along with the catalytic residues (Tyr343, and His235) of Endoribonuclease (NSP15) protein. CONCLUSION: The present study gives three-way options either by blocking S proteins or ACE2 receptor proteins or inhibiting RdRp to counter any effect of COVID-19 by macrolide and could be useful in the treatment of COVID-19 till some better option available.


Subject(s)
COVID-19 , Anti-Bacterial Agents/pharmacology , Antiviral Agents , Humans , Macrolides/pharmacology , Protein Binding , SARS-CoV-2
5.
Curr Med Chem ; 28(12): 2392-2408, 2021.
Article in English | MEDLINE | ID: covidwho-745092

ABSTRACT

The last couple of months have witnessed the world in a state of virtual standstill. The SARS-CoV-2 virus has overtaken the globe to economic and social lockdown. Many patients with COVID-19 have compromised immunity, especially in an aged population suffering from Parkinson 's disease (PD). Alteration in dopaminergic neurons and deficiency of dopamine in PD patients are the most common symptoms affecting 1% population above the age of 60 years. The compromised immune system and inflammatory manifestation in PD patients make them an easy target. The most common drugs under trial for COVID-19 are remdesivir, favipiravir, chloroquine and hydroxychloroquine, azithromycin along with adjunct drugs like amantadine with some monoclonal antibodies. Presently, clinically US FDA approved drugs in PD include Levodopa, catechol-O-methyl transferase (COMT) inhibitors, (Entacapone and Tolcapone), dopamine agonists (Bromocriptine, Ropinirole, Pramipexole, and Rotigotine), monoamine oxidase B (MAO-B) inhibitors (Selegiline and Rasagiline), amantadine and antimuscarinic drugs. The drugs have established mechanisms of action on PD patients with known pharmacodynamics and pharmacokinetic properties along with dose and adverse effects. Conclusion and relevance of this review focus on the drugs that can be tried on PD patients with SAR CoV-2 infection, in particular, amantadine that has been approved by all the developed countries as a common drug possessing both antiviral properties by downregulation of CTSL, lysosomal pathway disturbance and change in pH necessary to uncoat the viral proteins and anti- Parkinson properties. To deal with the significant prognostic adverse effect of SARS-CoV-2 on PD, the present-day treatment options, clinical presentation and various mechanisms are the need of the hour.


Subject(s)
COVID-19 , Parkinson Disease , Pharmaceutical Preparations , Aged , Antiparkinson Agents/therapeutic use , Catechol O-Methyltransferase , Communicable Disease Control , Humans , Middle Aged , Parkinson Disease/drug therapy , SARS-CoV-2
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