Synthesis, characterization, molecular docking and biological evaluation of Schiff Base derivatives of cefpodoxime.

Synthesis of new Cefpodoxime derivatives via Schiff Bases mechanism and the efficiency of their antimicrobial and antiviral activities were addressed. They were analyzed for structural validation by using spectroscopic techniques using FTIR, 1HNMR, and 13CNMR. Molecular docking against IBV Virus papain-like protease (PLPro) was done with Auto dock tools against compounds having excellent IC50 values against IBV (Corona Class) virus. All derivatives showed strong zone of inhibition ranges from (55 ± 2.0 to 70 ± 0.8 mm) against E. coli. Compounds 1,2,4 and 6 derivatives showed remarkable activity against Stenotrophomonas maltophilia and Serratia marcescens. But For most the newly synthesized derivatives C 1 (64 ± 1.60), C 3 (32 ± 0.80), and C 8 (64 ± 1.60) showed potential IC50 values against two variants of Corona class viruses i.e. Avian Influenza (H9) and Avian corona (IBV) viruses. The current study revealed that newly synthesized Schiff Bases possessed strong anti-viral potential. Further studies may make a breakthrough in medical sciences to tackle latest challenges such as Corona Virus Diseases.

Impact of the SARS-CoV-2 pandemic on vaccine-preventable disease campaigns.

BACKGROUND: The COVID-19 pandemic has contributed to the widespread disruption of immunization services, including the postponement of mass vaccination campaigns. METHODS: In May 2020, the World Health Organization and partners started monitoring COVID-19-related disruptions to mass vaccination campaigns against cholera, measles, meningitis A, polio, tetanus-diphtheria, typhoid, and yellow fever through the Immunization Repository Campaign Delay Tracker. The authors reviewed the number and target population of reported preventive and outbreak response vaccination campaigns scheduled, postponed, canceled, and reinstated at 4 time points: May 2020, December 2020, May 2021, and December 2021. FINDINGS: Mass vaccination campaigns across all vaccines were disrupted heavily by COVID-19. In May 2020, 105 of 183 (57%) campaigns were postponed or canceled in 57 countries because of COVID-19, with an estimated 796 million postponed or missed vaccine doses. Campaign resumption was observed beginning in July 2020. In December 2021, 77 of 472 (16%) campaigns in 54 countries, mainly in the African Region, were still postponed or canceled because of COVID-19, with about 382 million postponed or missed vaccine doses. INTERPRETATION: There is likely a high risk of vaccine-preventable disease outbreaks across all regions because of an increased number of susceptible persons resulting from the large-scale mass vaccination campaign postponement caused by COVID-19.

Impact of the SARS-CoV-2 pandemic on routine immunisation services: evidence of disruption and recovery from 170 countries and territories.

BACKGROUND: The SARS-CoV-2 pandemic has revealed the vulnerability of immunisation systems worldwide, although the scale of these disruptions has not been described at a global level. This study aims to assess the impact of COVID-19 on routine immunisation using triangulated data from global, country-based, and individual-reported sources obtained during the pandemic period. METHODS: This report synthesised data from 170 countries and territories. Data sources included administered vaccine-dose data from January to December, 2019, and January to December, 2020, WHO regional office reports, and a WHO-led pulse survey administered in April, 2020, and June, 2020. Results were expressed as frequencies and proportions of respondents or reporting countries. Data on vaccine doses administered were weighted by the population of surviving infants per country. FINDINGS: A decline in the number of administered doses of diphtheria-pertussis-tetanus-containing vaccine (DTP3) and first dose of measles-containing vaccine (MCV1) in the first half of 2020 was noted. The lowest number of vaccine doses administered was observed in April, 2020, when 33% fewer DTP3 doses were administered globally, ranging from 9% in the WHO African region to 57% in the South-East Asia region. Recovery of vaccinations began by June, 2020, and continued into late 2020. WHO regional offices reported substantial disruption to routine vaccination sessions in April, 2020, related to interrupted vaccination demand and supply, including reduced availability of the health workforce. Pulse survey analysis revealed that 45 (69%) of 65 countries showed disruption in outreach services compared with 27 (44%) of 62 countries with disrupted fixed-post immunisation services. INTERPRETATION: The marked magnitude and global scale of immunisation disruption evokes the dangers of vaccine-preventable disease outbreaks in the future. Trends indicating partial resumption of services highlight the urgent need for ongoing assessment of recovery, catch-up vaccination strategy implementation for vulnerable populations, and ensuring vaccine coverage equity and health system resilience. FUNDING: US Agency for International Development.

Synthesis, kinetics, structure-activity relationship and in silico ADME studies of new diazenyl azo-phenol derivatives against urease, SARS-CoV-2 main protease (Mpro) and ribosomal protein S1 (RpsA) of Mycobacterium tuberculosis

In the present study, a new series of diazenyl azo-phenol derivatives (TC-1 to TC-8) have been synthesized via diazo-coupling approach between substituted aromatic amines and phenol derivatives produced azo–phenol compounds in moderate to good yields (40-80%). The appearance of characteristic prominent peak of azo derivatives i.e. N=N peak at 1500-1400cm−1 and disappearance of NH2 stretch at 3500-3200 cm−1, presence of a broad OH stretch in the range of 3300-3000 cm−1 in FTIR spectra, while presence of OH peak in spectral range of 15-10 ppm and aromatic protons in the region of 8.0-6.0 ppm and disappearance of NH2 peak in 5.0-4.0 spectral region in 1H-NMR spectra confirms the synthesis of new diazenyl azo-phenol derivatives. Similarly, appearance of carbon attached with -N=N- group in the range of 149-144 ppm, C−OH in the range of 164-162 ppm, C−N of pyridine ring at 175 ppm, aromatic carbons at 140-108 ppm while aliphatic carbons at 21-20 ppm in 13C-NMR spectra give strong indication of synthesis of proposed compounds and HRMS also confirmed the masses of proposed structure of diazenyl azo-phenol derivatives. In case of urease inhibition potential, the in vitro results suggested that the compound TC-6 (IC50 value 0.62±0.04 µM) to be most active compared to the standard drug thiourea (IC50 value 21.44±0.78 µM), kinetic analysis revealed that TC-6 behaved as a mixed-type inhibitor with irreversible mode of action. The SAR showed the stable docked complex due to the presence of dihydroxy hydrogen atoms in TC-6 (-6.01 kcal/mol) and strong binding interactions with the active site residues of the target protein urease (3LA4). The detailed in silico analysis of the diazenyl azo-phenol derivatives (TC-1 to TC-17) against the ribosomal protein S1 (RpsA) of Mycobacterium tuberculosis (4NNI) and main protease (Mpro) of SARS-CoV-2 (6LU7) was also performed and SAR showed that among all the docked compounds, TC-6 and TC-9 showed best docked conformational poses by exhibiting strong interactions with the active site residues of the target proteins (4NNI & 6LU7) with minimum binding energy values i.e. -5.36 kcal/mol and -4.84 kcal/mol respectively. The ADME calculations showed that the synthesized ligands quietly obey rule of five without any considerable violations.