Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), initially originated in China in year 2019 and spread rapidly across the globe within 5 months, causing over 96 million cases of infection and over 2 million deaths. Huge efforts were undertaken to bring the COVID-19 vaccines in clinical development, so that it can be made available at the earliest, if found to be efficacious in the trials. We developed a candidate vaccine ZyCoV-D comprising of a DNA plasmid vector carrying the gene encoding the spike protein (S) of the SARS-CoV-2 virus. The S protein of the virus includes the receptor binding domain (RBD), responsible for binding to the human angiotensin converting enzyme (ACE-2) receptor. The DNA plasmid construct was transformed into E. coli cells for large scale production. The immunogenicity potential of the plasmid DNA has been evaluated in mice, guinea pig, and rabbit models by intradermal route at 25, 100 and 500µg dose. Based on the animal studies proof-of-concept has been established and preclinical toxicology (PCT) studies were conducted in rat and rabbit model. Preliminary animal study demonstrates that the candidate DNA vaccine induces antibody response including neutralizing antibodies against SARS-CoV-2 and also provided Th-1 response as evidenced by elevated IFN-γ levels.
In a sample of 1000 consecutive malignant neoplasms in Saudis resident in the Western Region of Saudi Arabia, malignant lymphoma was the commonest of the life‐threatening malignancies. The differences between malignant lymphoma in this sample and Western series include the greater frequency of lymphoma; the tendency for reticulum cell and poorly differentiated lymphomas to present as abdominal lesions; the earlier peak of prevalence of Hodgkin's disease, and the dissimilar proportions of its subtypes. The distribution of cancers in the gastrointestinal tract in our sample is almost the reverse of that encountered in the West in that cancer of the mouth and esophagus were more common than cancer of the lower intestinal tract. Lung cancer was relatively uncommon. The smoking habit is not so prevalent in Saudi Arabia as in the West and there is a need to maintain this situation by discouraging smoking. Cancer of the breast was by far the commonest major malignancy in the female, although most Saudi women have their first child early in their reproductive life. Skin cancers proved to be the most prevalent malignancy, and of these squamous cell carcinoma was the most common. The biases that affect studies such as ours in Saudi Arabia are stressed.
In an effort to discover potent antibacterials based on the entropically favored "bioactive conformation" approach, we have designed and synthesized a series of novel tricyclic molecules mimicking the conformationally constrained structure of the oxazolidinone antibacterial, Linezolid 1. The structure 3 obtained by this approach was synthesized and found to be moderately active against a panel of Gram-positive organisms tested. Further introduction of a fluorine atom in the aromatic ring of compound 3 as in Linezolid resulted in some excellent compounds possessing potent antibacterial activity. The thus obtained lead molecule 16 was further fine-tuned by structure-activity relationship studies on the amide functionality leading to a number of novel tricyclic oxazolidinone derivatives. Some particularly interesting compounds include the thioamides 36 and 37, thiocarbamate 41, and thiourea 45. The in vitro activity results of amide homologues of 16 (compounds 25-30) revealed that compounds up to four carbon atoms on the amide nitrogen retain the activity. In general, thioamides and thiocarbamates are more potent when compared to the corresponding amides and carbamates.
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), initially originated in China in year 2019 and spread rapidly across the globe within 5 months, causing over 96 million cases of infection and over 2 million deaths. Huge efforts were undertaken to bring the COVID-19 vaccines in clinical development, so that it can be made available at the earliest, if found to be efficacious in the trials. We developed a candidate vaccine ZyCoV-D comprising of a DNA plasmid vector carrying the gene encoding the spike protein (S) of the SARS-CoV-2 virus. The S protein of the virus includes the receptor binding domain (RBD), responsible for binding to the human angiotensin converting enzyme (ACE-2) receptor. The DNA plasmid construct was transformed into E. coli cells for large scale production. The immunogenicity potential of the plasmid DNA has been evaluated in mice, guinea pig, and rabbit models by intradermal route at 25, 100 and 500μg dose. Based on the animal studies proof-of-concept has been established and preclinical toxicology (PCT) studies were conducted in rat and rabbit model. Preliminary animal study demonstrates that the candidate DNA vaccine induces antibody response including neutralizing antibodies against SARS-CoV-2 and also provided Th-1 response as evidenced by elevated IFN-γ levels.
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