Sexual contact is the most common route of HIV transmission, and the concurrent presence of sexually transmitted infections (STIs) such as Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (gonococcus, GC) is known to increase the HIV risk. Antibiotic treatment decreases the incidence of STIs but not HIV. CT and GC activate Toll-like receptors (TLRs) 2 and 4, which act as sensors of microbial infection are critical for initiating immune responses to control infection. We have previously shown that GC enhances HIV infection of primary resting CD4+ T cells through activation of TLR2 but not TLR4. In this study, we determined the effect of live and fixed CT and different species of lactobacilli including L. jensenii and L. reuteri on HIV infection of freshly isolated PBMCs. We found that pretreatment of freshly isolated PBMCs with fresh or fixed CT, but not lactobacilli, promoted HIV infection of freshly isolated CD4+ T cells. Together with our previous reports, we concluded that STIs such as CT and GC but not commensal bacteria like lactobacilli enhanced HIV infection, possibly through immune activation. Importantly, the enhancement effect of fixed CT on HIV infection may explain the failure of antibiotic treatments to reduce the HIV incidence. Combined strategies to inhibit STI growth and STI-mediated mucosal immune activation should be considered for HIV prevention in the settings of STIs.
Brilacidin (PMX-30063), a non-peptide defensin-mimetic small molecule, inhibits SARS-CoV-2 viral infection but the anti-viral mechanism is not defined. Here we determined its effect on the specific step of the viral life cycle. Brilacidin blocked SARS-CoV-2 infection but had no effect after viral entry. Brilacidin inhibited pseudotyped SARS-CoV-2 viruses expressing spike proteins from the P.1 Brazil strain and the B.1.1.7 UK strain. Brilacidin affected viral attachment in hACE2-dependent and independent manners depending on the concentrations. The inhibitory effect on viral entry was not mediated through blocking the binding of either the spike receptor-binding domain or the spike S1 protein to hACE2 proteins. Taken together, brilacidin inhibits SARS-CoV-2 infection by blocking viral entry and is active against SARS-CoV-2 variants.
AbstractBackgroundClinical presentation, hospital admission and outcome of COVID-19 pandemic are different from one country to another. So every country should have their own data regarding COVID-19.Subjects and MethodsThis was an online cross-sectional survey, carried out in RT-PCR positive COVID-19 adult patient. A preformed questionnaire adapted in Google form and circulated through online to collect data. Informed consent was ensured before participation in this study.ResultsWe have studied of 305 RT-PCR positive COVID-19 patients, mean age was 36.32 (+/− 12.369) years with male predominance and majority were doctor 46.9%. 48.8% of the patient’s family members affected along with them. After COVID-19 pandemic 31.7% did not go out of their house. For prevention 72.4%)of the patients used mask and 38.8% used hand gloves during outing. 28.7% reported to be affected while working in hospital, 21.8%were affected in their office. Fever (80.1%), cough (57.7%), pain in throat (50.8%), rhinitis (45.9%) and loss of smell (45%) & taste sensation (45.6%) were the most common symptoms. Sample was given average 3 (+/− 3.384) days after onset of the symptoms and report was delivered average 4.57 days after giving sample. After getting result 32.1% of the patients seek treatment in telemedicine and 23% directly consulted in Government hospital, only 2% reported to be treated by the Government designated telephone number. 73.1% of the patient took both steam inhalation and warm water gargling. Paracetamol and antihistamine was the most commonly use drugs 69.8% and 71.5% respectively, besides 47.5% took ivermectin, 41.6% took azithromycin, 35.1% steroid, 34.8% took doxycyclin and 21.6% hydroxychloroquine. Among the patients only 20.3% needed hospital admission. The patients admitted in hospital average 5 (+/-3.922) days after onset of symptoms and hospital staying was 9.2 days (average). Breathless (54.83%) was the major cause of hospital admission and 19.35% patients admitted due to fear. 14% patients needed oxygen and average duration of oxygen was 4.84 days. 81.3% patients has taken oxygen in hospital and 18.8% at their home. Among the patient 2.2% needed ICU and artificial ventilation needed for 1.1% patients. The patients recovered after 17.74 days (average) from the onset of symptom. COVID-19 became negative (RT-PCR) at15th day from onset of symptom. 91.8%) were in mental stress to become the cause of infection spread to other family members, 20.7%) reported that they were anxious that they would not get oxygen or ICU if required and 27.9% were suffering from fear of death. Weakness was the most common post disease symptom in 57.4% cases. Average time required for coming back to normal life was 21.59 days (+/-7.901) ranging a wide range from 5 to 60 days.ConclusionCOVID-19 patients were mostly male, health worker. Fever, cough, pain in throat were most common symptoms. Hospital admission required in only one-fifth cases and ICU required for only 2% patients. Weakness was the most common post disease symptom.
