Structure-based drug designing and immunoinformatics approach for SARS-CoV-2.

The prevalence of respiratory illness caused by the novel SARS-CoV-2 virus associated with multiple organ failures is spreading rapidly because of its contagious human-to-human transmission and inadequate globalhealth care systems. Pharmaceutical repurposing, an effective drug development technique using existing drugs, could shorten development time and reduce costs compared to those of de novo drug discovery. We carried out virtual screening of antiviral compounds targeting the spike glycoprotein (S), main protease (Mpro), and the SARS-CoV-2 receptor binding domain (RBD)-angiotensin-converting enzyme 2 (ACE2) complex of SARS-CoV-2. PC786, an antiviral polymerase inhibitor, showed enhanced binding affinity to all the targets. Furthermore, the postfusion conformation of the trimeric S protein RBD with ACE2 revealed conformational changes associated with PC786 drug binding. Exploiting immunoinformatics to identify T cell and B cell epitopes could guide future experimental studies with a higher probability of discovering appropriate vaccine candidates with fewer experiments and higher reliability.

Comparative efficacy of intralesional verapamil hydrochloride and triamcinolone acetonide in hypertrophic scars and keloids.

There is not much level 1 evidence based literature to guide management of hypertrophic scars and keloids despite an array of therapeutic modalities at disposal. Intralesional (i/l) triamcinolone injections have remained a gold standard in non surgical management. Sporadic reports on use of i/l verapamil suggest its efficacy. Since verapamil has not found sufficient mention as an effective alternative modality, it was decided to undertake a randomized study which could also address some additional clinical parameters. A randomized, parallel group and observer blinded comparison with 40 patients (48 scars) was carried out to compare the effects of i/l triamcinolone (T) (22 scars) and verapamil injections (V) (26 scars). 1.5 ml was the maximum indicative volume decided in the study protocol for both the drugs (triamcinolone @40 mg/ml and verapamil @ 2.5 mg/ml). Patients included were aged between 15-60 years with scars ranging between 0.5-5 cm (but total area roughly <6 cm(2)), and scars under 2 years duration. Patients with keloidal diathesis were excluded. Injections were scheduled every three weeks until complete flattening of the scar or eight sessions, which ever came earlier. No concomitant therapies like massage, silicone gel or pressure garments were used. Scar evaluation at each stage was done by serial photographic records as well as by Vancouver Scar Scale (VSS). Comparative survival analysis between the two drugs was done using Kaplan Meier curves, and VSS scores were analyzed using Wilcoxon test and log rank test. Mean zero VSS scores were achieved with treatments in respect of scar height (T-12 weeks, V-21 weeks), vascularity (T-15 weeks, V-18 weeks) and pliability (T-15 weeks, V-21 weeks). The improvement in scar vascularity and pliability kept pace with decrease in scar height, in both the groups. There was not much difference in the rate of change of scar pigmentation with either drug but almost 60% patients in both the groups regained normal pigmentation. Our study adds to evidence of verapamil's capability in flattening the raised scars. With an extremely low cost and fewer adverse effects it deserves better positioning in the wide armamentarium against hypertrophic scars. It also offers several therapeutic possibilities to alternate with triamcinolone or be used simultaneously in larger (or multiple) scars.

A four arm, double blind, randomized and placebo controlled study of pregabalin in the management of post-burn pruritus.

Post-burn itch is a distressing symptom in burns rehabilitation and its treatment often proves frustrating for the patient and the multidisciplinary burns team. Traditionally, the mainstay of antipruritic therapy for decades has been antihistamines and massage with emollients. With a better understanding of the neurophysiology of itch emerged a new dimension in the treatment of post-burn pruritus. Gabapentin, a centrally modulating anti-epileptic agent and α2δ ligand, proved in clinical trials to be immensely better in the treatment of post-burn pruritus. Pregabalin is a newer structural analog of gabapentin. It has a much better anxiolytic effect and pharmacokinetic profile as compared to gabapentin. The current study was initiated to specifically study the role of pregabalin in relieving post-burn itch as this has never been investigated before. This double blind, randomized and placebo controlled study had four arms and was carried out on 80 adult patients (20 each). The four arms were: pregabalin, cetirizine with pheniramine maleate, combination of pregabalin, cetirizine and pheniramine maleate, and placebo (vit. B comp.). Massage with coconut oil was integral to all groups. Drug dosage was determined by initial VAS (visual analog scale) scores. All groups matched in demographic data and initial VAS scores. VAS scores were evaluated over next 28 days (days 3, 7, 14, 21 and 28). In patients with mild itch (VAS scores 2-5) or moderate itch (VAS scores 6-8) near complete remission of itch was seen in combination group and pregabalin group where the response was comparable and close to 95%. This was significantly better response than antihistaminic combination or massage alone. However, massage alone was sufficient in decreasing mean scores in mild itch, in a large percentage of patients. Amongst the patients with severe itch (VAS scores 9-10), 3/6 and 6/7 patients dropped out of trial in the antihistaminic and placebo groups, respectively. Combination therapy and pregabalin alone had exactly similar decrease in itch scores by day 28 (78.9%). This far exceeded the response in the antihistaminic and placebo groups (23.9% and 9.2% respectively). We conclude that moderate to severe pruritus (VAS 6-10) should be treated with a systemic, centrally acting agent like pregabalin or gabapentin to eliminate itch or bring it down to tolerable limits. Patients with mild itch having VAS scores between 4 and 5 may be better served with addition of pregabalin even if massage and antihistaminics can control post-burn itch to a reasonable extent because of quicker, predictable and complete response, along with anxiolysis.

A comparative analysis of liquefied petroleum gas (LPG) and kerosene related burns.

Previous studies from our department reflected a trend of decreasing incidence of burns culminating from rising income levels, which were bringing about a change in the cooking fuel in many urban households [1,2]. These studies also indicated a changing scenario of increased incidence of burns from LPG mishaps [2]. In the absence of much information on the subject we felt it rather imperative to comparatively study the pattern of burn injuries resulting from LPG and kerosene. This prospective study was conducted on the clinical database of consecutive patients admitted with burns sustained due to LPG and kerosene from 1st January 2009 to 31st May 2010 (17 months). Data recorded for each patient included; age, gender, religion, socioeconomic status, literacy level, type of family unit, marital status, type of dwelling unit, mode of injury and its exact mechanism, place of incident, level of cooking stove, extent of burns (%TBSA), presence of features of inhalation injury, number of patients affected in a single mishap, size of LPG cylinder used, length of hospital stay and mortality. Of 731 flame burn patients in this study, 395 (54%) were due to kerosene burns and 200 (27.4%) from LPG mishaps. Significantly, the majority of injuries, in both the groups, occurred in lower middle class families living as nuclear units, in a single room dwelling, without a separate kitchen. Majority of LPG burns (70.5%, 141 patients) resulted from a gas leak and 25.5% were from cooking negligence (51 patients). 50.5% of kerosene accidents were from 'stove mishaps' and 49% due to cooking negligence. In all kerosene accidents the stove was kept at floor level but in LPG group 20.6% had the stove placed on a platform. There was a slight difference in mean TBSA burns; 51% in kerosene group compared to 41.5% TBSA in LPG group. There were nine episodes in LPG group in which there were more than three burn victims admitted for treatment. Very importantly, 77% patients in LPG group were from a large cylinder (14.2 kg), which uses a rubber connecting tube. Mortality in kerosene group (50.6%) was far higher than in LPG group (33.5%). This study, from 200 LPG burn admissions, for the first time details the profile from LPG mishaps. It is very interesting to note that of all burns in the world the inequitable distribution bias towards LMICs (low and middle income countries) extends further towards low middle class families within the LMIC. A major risk factor is constrained living condition of a single room dwelling unit. Almost all burns from LPG mishaps were potentially preventable if more care had been practiced to ensure safety. Since majority of LPG mishaps were from gas leaks, either from the rubber tube (Fig. 1) or the stove valve, the observation of floor level cooking in 79.4% of LPG cases may be an economic compulsion of a single room dwelling unit without much impact on the injury pattern. The small LPG cylinder (5 kg) in which the burner is placed directly over the cylinder, as one unit without a connecting tube, is safer because it reduces the chances of a gas leak from an ill-fitting or a cracked rubber connecting tube (Fig. 2).

Burns and injuries from non-electric-appliance fires in low- and middle-income countries Part II. A strategy for intervention using the Haddon Matrix.

A large proportion of burns in developing countries are related to the nature of domestic appliances used for cooking, heating, and lighting. Our overview of the problem elucidated the need for better surveillance with epidemiologic studies, which will more accurately assess the true incidence in vulnerable populations. This paper will create a framework for envisaging new approaches to the problem and begin to evaluate the strengths and weaknesses of proposed interventions. We used the Haddon Matrix to accumulate proposed interventions that encompass a pre-event, event, and post-event timeline. We propose an initial strategic outline plan for interventions based on values that are suited to the problem and the setting, are culturally appropriate, and can be employed in a reasonable period of time for a sustained period to ensure success. Recommended action steps include promoting the use of alternative energy sources, encouraging an integrated approach to finding interdisciplinary solutions, devising a better system of kerosene containerization, re-engineering appliance designs, legislating for enforcement of health and safety standards, taking a holistic approach through government inter-departmental collaboration, formally discouraging corruption, encouraging ventilation of cooking or living areas, implementing building codes, educating consumers, and training caregivers and health and emergency workers.