Potential Drugs for the Treatment of COVID-19: Synthesis, Brief History and Application.

Coronaviruses (CoVs) belong to the Betacoronavirus group, an unusually large RNA genome characterized by club-like spikes that project from their surface. An outbreak of a novel coronavirus 2019 (nCOVID-19) already showed a unique replication strategy and infection that has posed significant threat to international health and the economy around the globe. Scientists around the world are investigating few previously used clinical drugs for the treatment of COVID-19. This review provides synthesis and mode of action of recently investigated drugs like Chloroquine, Hydroxychloroquine, Ivermectin, Selamectin, Remdesivir, Baricitinib, Darunavir, Favipiravir, Lopinavir/ ritonavir and Mefloquine hydrochloride that constitute an option for COVID-19 treatment.

Photodynamic activity and photoantimicrobial chemotherapy studies of ferrocene-substituted 2-thiobarbituric acid.

A ferrocene-substituted thiobarbituric acid (FT) has been synthesized to explore its photophysical properties and photodynamic and photoantimicrobial chemotherapy activities. FT has an intense metal-to-ligand charge transfer (MLCT) band at ca. 575 nm. The ferrocene moiety of FT undergoes photooxidation to form a ferrocenium species which in turn produces hydroxyl radical in an aqueous environment, which was confirmed via the bleaching reaction of p-nitrosodimethylaniline (RNO). FT exhibits efficient PDT activity against MCF-7 cancer cells with an IC50 value of 5.6 µM upon irradiation with 595 nm for 30 min with a Thorlabs M595L3 LED (240 mW cm-2). Photodynamic inactivation of Staphylococcus aureus and Escherichia coli by FT shows significant activity with log reduction values of 6.62 and 6.16 respectively, under illumination for 60 min at 595 nm. These results demonstrate that ferrocene-substituted thiobarbituric acids merit further study for developing novel bioorganometallic PDT agents.

Serological study of rickettsial diseases in human and rodent population in Chittoor dist. (A.P.).

In India the presence of Rickettsial disease in human is documented in many states however, the data on presence of Rickettsial infection in Andhra Pradesh is very scare. Therefore, a study was undertaken in Chittoor district (A.P.) to see the prevalence of Rickettsial infection in human and rodent population. 3-5 ml of human blood samples were collected from the patients attending the nearest hospitals of Tirumala, Tirupathi, Palmner and Chittoor areas. Live rodents were trapped and blood samples were collected from them during January and February 2008. Sera was separated and tested by Weil Felix test. Two hundred human sera samples were tested. Of these 39 samples were found reactive with Weil Felix antigen. Of the 39 reactive, 31 were male and 8 female. All the human samples were showing reactivity at 1:20 dilution. Out of the 343 rodents samples tested, only 24 samples were showing reactivity. These were reactive at 1:20, 1:40 and 1:80 dilutions with different types of Weil Felix antigens. Eight rodent sera samples were having titer 1:80 with Proteus OXK which is suggestive of presence of Scrub typhus in this region.

Insulin resistance and beta cell function as prognostic indicator in multi-organ dysfunction syndrome.

Insulin resistance (IR) is a major factor in the pathogenesis of sepsis. Critically ill patients with multi-organ dysfunction syndrome (MODS), diagnosed as per modified Acute Physiology and Chronic Health Evaluation II (modified APACHE II) score criteria and admitted to the medical ward in our hospital, were assessed for IR and beta cell function by using the homeostasis model assessment A (HOMA-A) and HOMA-B models, respectively. Of 80 consecutive patients, 60 were followed up to day 7; 16 patients died and 4 did not agree to follow up. The mean value of IR in all the 80 patients studied on the day 1 of hospitalization was 6.67 +/- 10.65. The initial high values of serum insulin and IR were significantly reduced (p < 0.05) as these patients recovered from their critical illness. Of those who died, the first day mean insulin levels were high (13.80 +/- 14.72 micro/ml as well as IR 5.14 +/- 6.76 values), but they had statistically low beta cell function (46.45 +/- 433.64%) as compared to those who recovered (227.60 +/- 430.36%; p < 0.05). This suggests that, beta cell overexhaustion occurs in critically ill patients, because it was required to overcome the prevailing state of IR and has more bearing in patients having less than 4 organ failures. beta cell failure ensued from the onset in those who were more moribund and had more than four organs failing or those who died. IR and beta cell function are reliable indicators of the state of severity of critical illness, and they corroborated with mortality in patients with MODS.

Autoimmunity, insulin resistance and Beta cell function in subjects with low body weight type 2 diabetes mellitus.

In developing countries like India, the majority of Type 2 diabetics are non-obese, and many are "lean" with a body mass index (BMI) below 18.5. This type is referred to as "Low Body Weight Type 2 DM" (LB Type 2 DM). LB Type 2 DM are confused with Type 1 DM or late autoimmune diabetes in adults (LADA) due to their high blood glucose levels and early insulin-requiring state. We assessed pancreatic islet cell autoimmunity by using both glutamic acid decarboxylase 65 antibody (GADA) and anti-IA(2) antibody estimation in 23 patients with LB Type 2 DM and 10 age-matched normal weight (NW) Type 2 DM. Fasting blood glucose (FBG) and 2 hr postchallenge blood glucose (PGBG2) were significantly higher in LB (p < 0.05), while mean values of fasting insulin (24.47 +/- 73.15 muIU/mL vs. 13.4 +/- 16.54 muIU/mL, p > 0.7) and fasting C-peptide (180.81 +/- 357.08 pM/mL vs. 279.83 +/- 281.38 pM/mL, p > 0.5) in LB and NW respectively were not statistically different. All 23 LB and 10 NW subjects were GADA negative while IA(2) positivity was found in 1/23 and 1/10 cases, respectively. LB Type 2 DM revealed good beta cell function with homeostasis model assessment beta cells (HOMAB) values of 57.41 +/- 153.18 as compared to 44.74 +/- 56.24 (p > -0.2) in NW Type 2 DM. Insulin resistance as assessed by homeostasis model assessment insulin resistant (HOMA IR) was 13.50 +/- 42.83 and 5.68 +/- 6.90 (p > 0.6) in LB and NW Type 2 DM, respectively, suggesting that LB Type 2 DM are a phenotypic variant of Type 2 DM.

Echinococcal disease and mycobacterial infection.

The clinical and radiological features of five patients with echinococcal disease in whom mycobacterial infection was also present are described. Three had clinically significant disease due to Mycobacterium tuberculosis (two patients) and M. fortuitum-chelonae (one patient), whilst in two others secondary infection with M. gordonae had occurred. In all cases the mycobacterium infection was found within or close to the anatomical confines of the echinococcal disease, as determined clinically, radiologically or histologically, which suggested a saprophytic-supportive role of the hydatid cyst for the mycobacterium to survive. Mycobacterial disease should be borne in mind in patients with echinococcal disease who remain unwell despite apparently effective treatment for the hydatid cyst.