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Background: Mucormycosis, once a rare fungal disease, has now shown a surge in cases, and its epidemiology in India is intriguing. Rising incidence confers the necessity of defining the demography of the population at risk, early diagnosis, and recommendations for the management of mucormycosis in patients with coronavirus disease (COVID-19) infection. Aims: To study the clinico-epidemological profile, risk factors, and histopathological features of COVID-19-associated Mucormycosis (CAM). Setting and Design: This is a retrospective observational study. Material and Methods: Fifty-six biopsy specimens taken from patients of COVID-19 with clinical suspicion of mucormycosis were included. Results: Diabetes mellitus, corticosteroids, and oxygen therapy were the most common risk factors associated with CAM. The mean duration between the onset of symptoms of COVID-19 and onset of CAM was 25.2 ± 15.3 days. Rhino-orbito-cerebral mucormycosis (ROCM) was present in 24.5% of the cases, with a survival rate of 58.3%. Histopathology showed tissue invasion by branching broad-based, pale, fungal hyphae consistent with mucor in 49 (87.5%) cases. Inflammation was acute neutrophilic type in 61.2% of the patients with a survival rate of 63.33%. The survival rate with chronic non-granulomatous and chronic granulomatous was 100% and 81.8%, respectively. Conclusion: Keeping a high index of suspicion for mucormycosis in COVID-19 by all medical fraternities of the health community in the existence of risk factors is the need of the hour for prompt diagnosis. Biopsy of antral necrotic tissue should be performed immediately after suspicion for histopathological study to confirm the diagnosis of mucormycosis and predict prognosis depending on the type of inflammation incited, fungal morphology, load, and necrosis.
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Context: Coinfection and superadded infections in patients with coronavirus disease 2019 (COVID-19) has been reported on multiple series. The emerging second wave of the pandemic has come with a lot of changes, especially in developing countries like India. One of such changes is sudden, significant rise in mucormycosis cases. Aims: To find out clinicopathological association of invasive mucormycosis with COVID-19 infection status and immunocompromised state. Settings and Design: A cross-sectional study done at a tertiary care centre. Methods and Material: All cases admitted in the dedicated mucormycosis ward between 1-06-2021 and 15-06-2021 were included in the study. The cases were admitted with suspicion of mucormycosis. The histopathological results were correlated with KOH mount and radiological reports. The clinicopathological association of occurrence of mucormycosis in post-covid and non-COVID patients along with other risk factors. Statistical Analysis Used: Odds ratio, chi square test were used to find the association using MS Excel 2010 and SPSS. Results: Thirty-six (81.82%) cases were of the post-COVID status, and 8 cases were non-COVID status. Out of 36 post-COVID patients, 33 (91.67%) showed evidence of invasive mucormycosis and of 8 non-COVIDpatients, 7 had evidence of mucormycosis (odds ratio = 1.57). Out of the total diagnosed cases of mucormycosis, 21 (52.5%) patients were known cases of diabetes mellitus (DM), and 7 (17.5%) cases of newly diagnosed hyperglycemia. Thirty (75%) patients out of 40 had some form of immunocompromised state. This shows statistically significant association of DM and immunocompromised state with the occurrence of mucormycosis in post-COVID patients (chi square value2 = 6.891, P value = 0.008). Twenty-five patients had the history of steroid use during the treatment of COVID-19. Conclusions: The infection with COVID-19 definitely increases the odds of contracting mucormycosis, but most of the cases had diabetes mellitus. So, it is possible that COVID-19 virus predisposes individuals to invasive fungal infection by precipitating DM.
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The Galenic venous system plays a vital role in the drainage of blood from deeper parts of the brain. This venous system is contributed by many major veins. These veins are located closer to the pineal gland making the surgical approach in this region difficult. Any accidental injury or occlusion of the vein of Galen could lead to devasting results. Thus, studying the dimensions of the vein of Galen is more important. Hence, we aimed to evaluate the morphometry and trajectory to the vein of Galen. About 100 computed tomographic venography records were evaluated and the length, diameter of vein of Galen, angle between straight sinus and vein of Galen and distance from internal occipital protuberance and roof of fourth ventricle to vein of Galen were studied. The mean length and diameter of vein of Galen were 9.8±2.7 and 4.08±1.04 respectively. The mean angle between straight sinus and vein of Galen was 64.2°. The mean distance between external occipital protuberance and roof of fourth ventricle to vein of Galen were 52±6.9 and 33.3±4.5 respectively. No significant morphometric differences were observed between the age groups as well as between the sexs. The results obtained from this study may be helpful for the neurosurgeons in better understanding of the anatomy of the Galenic venous system and to adopt a safe surgical approach to improve the efficacy of the surgeries of the pineal gland and also in the region of vein of Galen.
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Background/Aim: Chronic pancreatitis (CP) is surgically treated in selected patient populations. Frey's procedure (FP) is the most commonly described procedure for CP with head mass. This study is being conducted to determine the long-term outcome and ef?cacy of FP in patients with CP in South India of various etiologies. Methods: This is a retrospective study of patients who underwent FP at our institution. Clinical features, perioperative ?ndings, and follow-up results were evaluated. A subgroup analysis of pain relief was performed between alcoholics and non-alcoholic groups and between patients receiving FP alone and FP with additional procedures. Of the 181 patients, alcohol was Results: the causative factor in 99 (54.69%), gallstones in 20 (11.04%), and idiopathic in 62 (34.25%). With a median follow-up of 43.49 months (range 12-72 months), 78 (43.09%) patients experienced complete pain relief. Due to persistent pain and the presence of preoperative diabetes mellitus (DM), pain relief in patients with postoperative complications was incomplete. New DM and exocrine dysfunction were reported in 25 years (13.81%) and 15 (8.28%) patients. Patients with a history of alcohol abuse, smoking, weight loss, and postoperative complications are associated with newly developed diabetes. FP is a Conclusion: safe surgical option for CP with acceptable perioperative complications and appropriate short-term and long-term pain management in properly selected patients. Continuous pain and preoperative DM were independent predictors of incomplete pain relief after FP. Symptoms associated with alcohol abuse, smoking, and weight loss were associated with the development of post-FP DM in the study population.
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Citrus is one of the major fruit crops in the world and widely recognized by their nutritional, organoleptic and health-related benefits of fresh fruit. The genetic diversity among the genus and independent changes in peel and pulp, make the definition of standard maturity indexes of fruit quality. Commercial maturity indexes in the citrus industry are usually based on peel coloration, soluble solids, pH but their relevance may differ among varieties and the specific requirements of the markets. Citrus fruits are excellent source of many phytochemical, including ascorbic acid, antioxidant, tannin, etc., which greatly contribute to the health-related benefits of citrus fruits. Criteria and definition of the main maturity indexes for citrus fruit worldwide are described, as well as changes during fruit maturation in key components affecting organoleptic and nutritional properties. Citrus fruits were analyzed at different maturity stages. This review is aimed to characterize the physiological maturity of the fruit across the different developmental stage which has not been well reported in literature till now.
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Background: Inflammatory bowel diseases (IBDs) mainly consist of Crohn's Disease (CD) and Ulcerative Colitis (UC). These two categories have overlapping histopathological features and sometimes it is difficult to diagnose them into distinct category and such biopsies are categorised as Inflammatory Bowel Disease (IBD-U). Recently, there has been an increase in interest to discover new biomarkers of IBD to differentiate UC and CD and predict their prognosis. Method: In the present study, 273 non-neoplastic colonic biopsies with clinicoendoscopic features of IBD were studied and categorized into UC (88; 32.3%) and CD (03; 1.1%) but a major chunk remained in category of IBD-U (182; 66.6%). 161 (58.9%) of these biopsies were then subjected to IHC for RB protein and ?-catenin and Serology for pANCA and ASCA was done in only 85 (31.13%) of these selected cases for identification of UC and CD on colonic biopsies. Result: 161 biopsies that were subjected to IHC analysis included 57 cases of UC, 03 cases of CD, and rest 101 cases of IBD-U. Out of 101 cases of IBD-U, 87 (86.13%) cases were reclassified as UC (61; 60.3%) and CD (14; 13.86%) on the basis of results of IHC and Serology. Conclusion: The two major tools IHC for ?-catenin and RB protein and the assay of serum ASCA and p-ANCA along with proper history and clinical presentation can act as a good adjunct to conventional H and E in subclassifying cases of IBD-U into UC and CD.
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Background: High-grade pelvic serous carcinoma is a common cause of death in women worldwide and India. Recent evidence has clearly implicated the changes in the mucosa of the fimbrial end of the fallopian tube in its pathogenesis. Objective: 1) To study histopathology features of surgically resected specimens of fallopian tubes received with non-neoplastic lesions of the uterus and ovary for the presence of any precursor lesions [secretory cell outgrowth (SCOUT), serous tubal intraepithelial lesion (STIL), p53 signatures, and serous tubal intraepithelial carcinoma (STIC)]. 2) To confirm the findings with immunohistochemistry. 3) To correlate the prevalence of precursor lesions with clinical parameters and benign lesions of the uterus and ovaries. Materials and Methods: Assessment of histopathological changes in 100 specimens of distal fallopian tubes was done using the sectioning and extensive examination of the fimbrial end (SEE-FIM) protocol. H and E stain followed by immunohistochemistry for Bcl-2, p53, and Ki-67. The statistical significance of the difference in the mean values of precursor areas was evaluated by an unpaired t-test. Results: Among 100 specimens taken on H and E, precursor lesions were suspected in 49% of the cases. SCOUT, suspicious for STIC, suspicious for STIC with areas of SCOUT, and unequivocal for STIC with areas of SCOUT were seen in 8%, 4%, 33%, and 4% of the cases, respectively. However, on IHC, SCOUTS were confirmed in 45% of the cases, p53 signature in 2%, STIL in 9%, and STIC in 4% of the cases. Conclusion: Sectioning and extensive examination of the fimbrial end (SEE-FIM) should be routinely done as it provides the opportunity to detect the early malignant changes. It may help in evolving the strategies for early detection, management, and reducing mortality.
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Study Design: Prospective case series Delayed wound healing is a significant concern, particularly in Introduction: complex wounds and the elderly with co-morbidities. It leads to pain, morbidity, prolonged treatment, and requires major reconstructive surgery, which imposes an enormous social and financial burden. Negative Pressure Wound Therapy (NPWT) was used to cover large wounds, decubitus ulcers, and open fractures that cannot be closed either primarily or secondarily and often require a complex reconstructive procedure to protect the injury. NPWT is an alternative method of wound management, which uses the negative pressure to prepare the wound for spontaneous healing or by lesser reconstructive options. We applied NPWT on pa Materials and Methodology: tients with open fractures, decubitus ulcers, neglected wounds, fasciotomies, and large wounds. Compared to the patented VAC system, ours include pre-sterilized PVA foam, cling drape (Surgiwear TM), nasogastric tube or an infant feeding tube, and a hospital wall suction. There Results: were three cases of soft tissue injury of the foot with wound defect, one case of fasciotomy for compartment syndrome, one case of the decubitus ulcer, one case of open fractures, and three cases of degloving injuries of the foot. In our study, the NPWT was changed every five days, the average number of NPWT changes was 3-4, length of time NPWT applied before the closure was 14-21 days. The most frequent coverage mode is Split Thickness Skin Graft obviating the need for more complex flaps and microvascular reconstructive procedures. Negative Conclusion: pressure therapy stabilizes the wound environment, reduces wound edema/bacterial load, improves tissue perfusion, and stimulates granulation tissue and angiogenesis. NPWT appears to be simple and more effective than conventional dressings for managing complex wounds, reducing wound volume, depth, treatment duration, and cost.
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Background: Dyspnoeic in the emergency department with multiple co-morbidities is a diagnostic challenge. Approximately 15-20% of acute dyspneic in the Emergency Department due to ADHF (acute decompensated heart failure) are misdiagnosed. B-type peptide (BNP) and its amino-terminal fragment (NT-proBNP) accurately identify HF in dyspnoeic patients. In the general population with dyspnoea, plasma pro-BNP concentrations are increased in left ventricular dilatation, hypertrophy, systolic dysfunction, or diastolic dysfunction but are unaffected by pulmonary dysfunction. Aims and Objectives: To study the relation between NT pro-BNP & echocardiographic findings in acute dyspnoeic patients, and the relation between NT pro-BNP and In-hospital Mortality. Materials and Methods: Source of data- Patients admitted to the Emergency Room or cardiac intensive care unit with a history of acute dyspnea in a tertiary cardiac care center in south India, meeting inclusion & exclusion criteria, were studied. Results: The study population is predominantly constituted of the elderly population. The most common co-morbid condition was hypertension. The present study uses an NT pro BNP level of 900pg/ml as the cut-off level. 78 patients were positive for the test. Echocardiography showed that 58% had LV systolic dysfunction, 60% had diastolic dysfunction. 42 patients had EF >55%, 10 patients between 55-45%, 33 patients between 44-30% and 15 patients had EF < 30%. Mortality rate was 6% in the whole study population. However, Mortality was seen in only NT pro-BNP positive group it was not statistically significant (p=0.46). Conclusions: NT pro-BNP correlates well with the worsening of LV systolic function; as the EF decreases, NT pro-BNP increases. Increase in NT pro-BNP levels has to be interpreted in the clinical context, and it is not a substitute for echocardiography for assessing cardiac abnormalities and dysfunction.
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Background: COVID-19 severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was declared Pandemic by the World Health Organization on January 30, 2020. Vaccination represents the best possibility to resolve this pandemic. The current global challenge is the immunization against the SARS-CoV-2. However, the adverse events following immunization (AEFI) of the corona vaccine remains unclear. Aim and Objectives: This observational study aims to represent an accountable data of the AEFI between Covaxin and Covishield in North Indian population. Materials and Methods: The hospital-based prospective and observational study was employed from January 2021 to December 2021 for detecting and monitoring of AEFI in adults. All population vaccinated either covishield or covaxin with both doses were enrolled in the study as targeted population. Post-vaccination vaccinated population were telephonic follow-up with prior consent. Results: A total of 1015 vaccinated individuals were included in this study for assessment of AEFI. After statistical analysis of AEFI between both vaccination at 24 h P = 0.13, 3–7 days 0.4 and complete AEFI P = 0.06 observed. There is no association that was found significant P < 0.05 with the incidence of AEFI. Conclusion: The short-term outcome has not attribute any serious AEFI. This study demonstrated that both vaccines were well-tolerated and safe in generalized population.
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Background: Safe disposal of expired medicines is a problem which is current area of intense discussion among policy makers. This project was conducted to explore the knowledge, attitudes, and practices (KAP) among hospital pharmacies and drug store owners about expired medicines and their disposal. The information generated could be used to plan proper and safe drug disposal practices. Aims and Objectives: This project was conducted to explore the KAP among hospital pharmacies and drug store owners about expired medicines and their disposal. The information generated could be used to plan proper and safe drug disposal practices. Materials and Methods: The target population for the current project were the pharmacies dispensing drugs to patients. Pharmacies situated in the hospitals were also covered in this survey. KAP survey is designed to explore the present concepts about a topic of public interest in the target population. Results: The present study was conducted in 373 participants. Most of the participants (88.37%) believed that expired drugs should be returned to manufacturers and proper disposition is the responsibility of pharmacists (72.6%). However, few others believed that it should be cumulative responsibility of nursing professionals and municipal corporations as well. Most of the pharmacists were of opinion that expiry date is fixed by regulatory body (56.0%) and depends on storage conditions (59.2%) of drugs. Conclusion: An innovative policy needs to be implemented by the health regulators to strengthen the existing drug disposal policies more effectively.
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In 2019, a new variant of coronavirus emerged that put the whole world on a standstill due to its unprecedented spread and morbidity. Since then, scientists have been working on several theories to explain the origin and pathogenesis of the virus. Over this period of time, it has been observed clinically that individual variation exists in the way this virus infects people, its symptomatology and sequelae. The pathophysiology is still unclear. This review was taken up to consolidate all the available information until date about current theories of etiopathogenesis with an understanding of potential therapeutic targets on the mechanisms. This review also highlights the gray areas that need to be addressed in the future. Research papers published up to December 7, 2020 were included based on a search on PubMed, Google Scholar, etc., to get the latest relevant literature on this topic. Coronavirus expresses differently in different individuals, affecting different organ systems, and having variable severity. However, the underlying pathogenic mechanisms are not completely understood. Due to the lack of definite curative therapy, it is essential to explore the basic pathophysiology so as to develop more effective and target-based therapies in the future.
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The medical education system in India is one of the largest in the world. Therefore, the quality of Indian medical education and the physicians it produces has implications on public health at large. Change is the necessity of evolution and growth. In this article, we address the challenges Indian undergraduate medical education faces and attempt to address them. The steps suggested are delineation of goals and objectives of education based upon the need of the country, adoption of innovative digital-based synchronous and asynchronous teaching, both in-person and digital learning methodology (hybrid model), early introduction of clinical postings, family adoption program, shortening the course of MBBS, problem-based learning, adjustments in the course structure, updating of course content, rationalizing assessment strategy, and emphasis on structured and skill-oriented internship.
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Background: Calcium supplementation during pregnancy has a proven potential to reduce adverse gestational outcomes, in particular by decreasing the risk of developing hypertensive disorders during gestation. Objective: to evaluate various factors influencing the consumption of iron folic acid and calcium tablets supplementation during pregnancy. Methodology: A community based analytical cross-sectional study was conducted among 200 women in the rural field practice area of Jhalawar. Data were collected by house to house visit and analysed using chi-square test. Results: Only 55.5% pregnant women have taken IFA tablets while 23.5% women have taken tablets of calcium during their pregnancy. IFA consumption were significantly associated with level of education of women and their husband, socio-economic class, type of family, number of ANC visits and presence of husband during those visits and mass media exposure Calcium consumption were also associated with level of education of women, socio-economic class, number of ANC visits and presence of husband during those visits. Conclusions: Consumption of IFA tablets was higher than the national level however calcium consumption was low. Emphasis should be given on early registration, multiple ANC visits, role of family and husband in caring of mother during pregnancy to improve consumptions of IFA and Calcium supplements.
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Background & objectives: The oropharyngeal (OP) and nasopharyngeal (NP) swab samples are the most recommended clinical specimens for detecting SARS-CoV-2 in an individual through the quantitative real-time reverse-transcriptase-polymerase chain reaction (rRT-PCR) method. The primary objective of this study was to compare the performance of NP and OP swabs for the diagnosis of COVID-19 among 2250 concomitant samples (1125 NP + 1125 OP) using rRT-PCR test. Methods: This study was conducted at a tertiary care hospital in southern India. The study compared the specificity and efficacy of the two samples (NP & OP swabs) in 1125 individuals suspected having COVID-19 infection. The rRT-PCR values from all the samples were compared based on gender, age group and viral load. The differences between unmatched proportion and matched proportion were analysed. Agreement between the two methods was assessed using Kappa statistic. Absolute sensitivity, specificity, positive and negative predictive values (PPV and NPV) for OP and NP swabs were analysed. Results: The study identified a fair degree of agreement between OP and NP swabs in diagnosis of COVID-19 (kappa = 0.275, P<0.001). There was also a fair degree of agreement between NP and OP swabs irrespective of gender, age or duration of symptoms. NP swabs had better sensitivity and NPV as compared to OP swabs, however, specificity and PPV were 100 per cent for both. Interpretation & conclusions: The present study showed that both OP and NP swabs had similar sensitivity and specificity for predicting the presence of SARS-CoV-2.
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Introduction: The patients with Type 2 diabetes Mellitus may often remain asymptomatic for a longer period of time. The Indian Diabetes Risk Score (IDRS), a simple screening tool for prediction of undiagnosed diabetes. Objective: Validation of IDRS with standard test for type 2 diabetes among urban population of Jhalawar, Rajasthan. Material and Methods: A Community based Cross-sectional study was carried out in urban field practice area of Department of Community Medicine, Jhalawar Medical College, Jhalawar, Rajasthan. The study was conducted using a two-stage sampling design. A predesigned, pretested proforma and Indian Diabetes Risk Score (IDRS) sheet was used to collect data from the study participants. The IDRS is based on four parameters: age, family history of diabetes, waist circumference and physical inactivity. Data was collected using the World Health Organization stepwise approach to surveillance (STEPS). Results: Among 450 participants, 12.7% participants were in low risk, 59.1% were in moderate risk and 28.2% were in high risk of developing diabetes according to IDRS score. IDRS score of ?60 turned out to be the best cut point for identifying undiagnosed diabetes with sensitivity 92.3% and specificity 82.6%. Positive Predictive value and Negative Predictive value were 47.3% and 98.5% respectively. Conclusion: Association of IDRS was found significant with diabetes. IDRS score of ?60 turned out to be the best cut point for identifying undiagnosed diabetes. IDRS is found valid screening tool for early detection of Diabetes.
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@#Introduction: Osteoarthritis (OA) is estimated to be the fourth leading cause of disability in the general population. It probably is the most common disease of joints in adults throughout the world. Knee OA accounts for more than 80% of the disease’s total burden and as per an estimate in US population, it affects at least 19% of adults aged 45 years and older. This was a randomised study aimed to evaluate the efficacy of platelet rich plasma (PRP) as a treatment modality for osteoarthritis knee in comparison to arthroscopic management. Materials and methods: This study was conducted from 2018 to 2020 at a tertiary care teaching hospital, under reference number ELMC&H/RCELL2019/39. A total of 70 patients of osteoarthritis knee with grade 2-3 according to the Kellgren-Lawrence classification were selected using computer generated random number among them 35 patients were subjected to arthroscopy (Group II) and 35 were administered platelet rich plasma injection (Group I) and evaluated at 3, 6 and 9 months of follow-up. Both the groups were assessed and scored with the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and Visual Analog Pain Scale (VAS) to compare pre-treatment and post-treatment values. As all the patients in the sample was followed-up, resulting into no loss of subjects. Result: Overall, percentage reduction in VAS score at 3 months, 6 months, and 9 months was 24.45±9.09, 18.45±11.60 and 8.29±14.19%, respectively in Group I and 18.96±5.85, 7.33±8.60 and 3.20±7.39%, respectively in Group II. A statistically significant difference between two groups was observed at 3- and 6-months’ time intervals only (p<0.05). Overall, percentage reduction in WOMAC score at 3 months, 6 months and 9 months was 24.03±11.41, 17.45±9.24, and 9.49±9.80%, respectively in Group I and 11.27±5.73, 5.70±4.78, and -0.13±5.06%, respectively in Group II. At all the three-time intervals, the difference between two groups was significant statistically (p<0.001). Conclusion: This study suggested that both PRP as well as arthroscopy provide a reduction in WOMAC and VAS scores for pain among cases of knee osteoarthritis. Most effective reduction is observed at three months follow-up which thereafter tends to diminish. Of the two modalities, PRP seemed to have an edge over arthroscopic debridement, however, this efficacy was more pronounced for KellgrenLawrence Grade 2 as compared to Grade 3.
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The future of Indian students who return as ‘foreign medical graduates’ (FMG) after training in certain countries is often uncertain. We collected data from newspapers, government resources and agencies involved in handling this issue. We analysed the current status of medical education in India, the Commonwealth of Independent States (CIS) and some neighbouring countries. Of approximately 1.4 million (14 lakh) students taking the National Eligibility cum Entrance Test (NEET), about 5.8% get admission in medical colleges. There are about 554 medical colleges in India with 82 550 MBBS seats, 51.9% seats belong to the government quota. Parents who send their children to a foreign country to do medicine spend ?1.5 million (15 lakh) tò4 million (40 lakh) against an estimated annual income of ?1.2 million (12 lakh) and the child spends 4–6 years in a foreign country. Of 38 150 FMGs who took the examinations conducted by the National Board of Examinations from 2015 to 2018, 18.9% passed the FMG examination mandatory for registration to practise medicine in India. The National Medical Commission is trying to solve this issue by removing the age bar for entry to MBBS and recommending lowering of fees for MBBS in government quota. Seeking graduation in medical colleges outside India may not be advisable for those from the middle/ low-income group of India.
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Surgery plays an important role in curative treatment of oesophageal carcinoma. Ivor-Lewis procedure modified by McKeown is the procedure of choice, which is an open approach. Here, we present our experience with a modified three-stage procedure i.e. right thoracoscopy, mini-laparotomy and cervical anastomosis, which shows that oncological procedures can be performed by minimally invasive procedures; this helps in reducing complications associated with open technique, especially pulmonary, without any oncological disadvantage for the patient. Thus, we propose that a minimally invasive approach is a significantly better technique for tumour resection, combined with neo adjuvant chemotherapy, in reducing hospital stay and improved quality of life.
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Of all known small molecules targeting human immunodeficiency virus (HIV) capsid protein (CA), PF74 represents by far the best characterized chemotype, due to its ability to confer antiviral phenotypes in both early and late phases of viral replication. However, the prohibitively low metabolic stability renders PF74 a poor antiviral lead. We report herein our medicinal chemistry efforts toward identifying novel and metabolically stable small molecules targeting the PF74 binding site. Specifically, we replaced the inter-domain-interacting, electron-rich indole ring of PF74 with less electron-rich isosteres, including imidazolidine-2,4-dione, pyrimidine-2,4-dione, and benzamide, and identified four potent antiviral compounds (