A Narrative Review of Existing Options for COVID-19-Specific Treatments

The new coronavirus disease 2019 (COVID-19) was declared a global pandemic in early 2020. The ongoing COVID-19 pandemic has affected morbidity and mortality tremendously. Even though multiple drugs are being used throughout the world since the advent of COVID-19, only limited treatment options are available for COVID-19. Therefore, drugs targeting various pathologic aspects of the disease are being explored. Multiple studies have been published to demonstrate their clinical efficacy until now. Based on the current evidence to date, we summarized the mechanism, roles, and side effects of all existing treatment options to target this potentially fatal virus.

In Vitro Comparison of the Internal Ribosomal Entry Site Activity from Rodent Hepacivirus and Pegivirus and Construction of Pseudoparticles

The 5′ untranslated region (5′ UTR) of rodent hepacivirus (RHV) and pegivirus (RPgV) contains sequence homology to the HCV type III internal ribosome entry sites (IRES). Utilizing a monocistronic expression vector with an RNA polymerase I promoter to drive transcription, we show cell-specific IRES translation and regions within the IRES required for full functionality. Focusing on RHV, we further pseudotyped lentivirus with RHV and showed cell surface expression of the envelope proteins and transduction of murine hepatocytes and we then constructed full-length RHV and RPgV replicons with reporter genes. Using the replicon system, we show that the RHV NS3-4A protease cleaves a mitochondrial antiviral signaling protein reporter. However, liver-derived cells did not readily support the complete viral life cycle.

Evaluation of the Risk of Clinical Deterioration among Inpatients with COVID-19

This study aims to assess the risk of severe forms of COVID-19, based on clinical, laboratory, and imaging markers in patients initially admitted to the ward. This is a retrospective observational study, with data from electronic medical records of inpatients, with laboratory confirmation of COVID-19, between March and September 2020, in a hospital from Juiz de Fora-MG, Brazil. Participants (n = 74) were separated into two groups by clinical evolution: those who remained in the ward and those who progressed to the ICU. Mann–Whitney U test was taken for continuous variables and the chi-square test or Fisher’s exact test for categorical variables. Comparing the proposed groups, lower values of lymphocytes ( p = <0.001) and increases in serum creatinine ( p = 0.009), LDH ( p = 0.057), troponin ( p = 0.018), IL-6 ( p = 0.053), complement C4 ( p = 0.040), and CRP ( p = 0.053) showed significant differences or statistical tendency for clinical deterioration. The average age of the groups was 47.9 ± 16.5 and 66.5 ± 7.3 years ( p = 0.001). Hypertension ( p = 0.064), heart disease ( p = 0.048), and COPD ( p = 0.039) were more linked to ICU admission, as well as the presence of tachypnea on admission ( p = 0.051). Ground-glass involvement >25% of the lung parenchyma or pleural effusion on chest CT showed association with evolution to ICU ( p = 0.027), as well as bilateral opacifications ( p = 0.030) when compared to unilateral ones. Laboratory, clinical, and imaging markers may have significant relation with worse outcomes and the need for intensive treatment, being helpful as predictive factors.

Natural Products with Inhibitory Activity against Human Immunodeficiency Virus Type 1

Infections caused by human immunodeficiency virus (HIV) are considered one of the main public health problems worldwide. Antiretroviral therapy (ART) is the current modality of treatment for HIV-1 infection. It comprises the combined use of several drugs and can decrease the viral load and increase the CD4+ T cell count in patients with HIV-1 infection, thereby proving to be an effective modality. This therapy significantly decreases the rate of morbidity and mortality owing to acquired immunodeficiency syndrome (AIDS) and prolongs and improves the quality of life of infected patients. However, nonadherence to ART may increase viral resistance to antiretroviral drugs and transmission of drug-resistant strains of HIV. Therefore, it is necessary to continue research for compounds with anti-HIV-1 activity, exhibiting a potential for the development of an alternative or complementary therapy to ART with low cost and fewer side effects. Natural products and their derivatives represent an excellent option owing to their therapeutic potential against HIV. Currently, the derivatives of natural products available as anti-HIV-1 agents include zidovudine, an arabinonucleoside derivative of the Caribbean marine sponge (Tectitethya crypta), which inhibits the reverse transcriptase of the virus. This was the first antiviral agent approved for treatment of HIV infection. Additionally, bevirimat (isolated from Syzygium claviflorum) and calanolide A (isolated from Calophyllum sp.) are inhibitors of viral maturation and reverse transcription process, respectively. In the present review, we aimed to describe the wide repertoire of natural compounds exhibiting anti-HIV-1 activity that can be considered for designing new therapeutic strategies to curb the HIV pandemic.

Survival of SARS-CoV-2 on Clothing Materials

In order to plan and execute proper preventative measures against COVID-19, we need to understand how SARS-CoV-2 is transmitted. It has been shown to remain infectious on surfaces from hours to days depending on surface type and environmental factors. The possibility of transmission through fur animals and contaminated pelts, along with the safety of those working with them, is a major concern. SARS-CoV-2 can infect minks and raccoon dogs and has spread to mink farms in numerous countries. Here, we studied the stability of SARS-CoV-2 on blue fox, Finn raccoon, and American mink pelt, fake fur, cotton, plastic, faux leather, and polyester and tested its inactivation by UV light and heat treatment. We detected infectious virus up to 5 days on plastic, up to 1 day on fake fur, less than a day on cotton, polyester, and faux leather, and even 10 days on mink fur. UV light failed to inactivate SARS-CoV-2 on pelts, most likely due to the mechanical protection by the fur. Hence, it should not be used to inactivate the virus on fur products, and its use for other surfaces should also be considered carefully. Heat treatment at 60°C for 1 h inactivated the virus on all surfaces and is a promising method to be applied in practice. This study helps prevent further spread of COVID-19 by increasing our understanding about risks of SARS-CoV-2 spread through contaminated clothing materials and giving important information needed to improve safety of those working in the production line as well as people using the products.

Risk Factors for Chikungunya Virus Outbreak in Somali Region of Ethiopia, 2019: Unmatched Case-Control Study

Background. Chikungunya virus is a ribonucleic acid (RNA) virus transmitted by a mosquito bite. Chikungunya virus outbreaks are characterized by rapid spread, and the disease manifests as acute fever. This study aimed at determining risk factors for chikungunya virus outbreak to apply appropriate prevention and control measures. Methods. Unmatched case-control study was performed to identify risk factors of chikungunya outbreak in Somali region of Ethiopia in 2019. Cases and controls were enrolled with 1 : 2 ratio. All cases during the study period (74 cases) and 148 controls were included in the study. Bivariate and multivariable analyses were implemented. The serum samples were tested by real-time polymerase chain reaction at Ethiopian Public Health Institute Laboratory. Results. A total of 74 chikungunya fever cases were reported starting from 19th May 2019 to 8th June 2019. Not using bed net at daytime sleeping (adjusted odds ratio (AOR): 20.8; 95% confidence interval (CI): 6.4–66.7), presence of open water holding container (AOR: 4.0; CI: 1.2–3.5), presence of larvae in water holding container (AOR: 4.8; CI: 1.4–16.8), ill person with similar signs and symptoms in the family or neighbors (AOR: 27.9; CI: 6.5–120.4), and not wearing full body cover clothes (AOR: 8.1; CI: 2.2–30.1) were significant risk factors. Conclusion. Not using bed net at daytime sleeping, presence of open water holding container, presence of larvae in water holding container, ill person with similar signs and symptoms in the family or neighbors, and not wearing full body cover clothes are risk factors for chikungunya virus outbreak.

No Detection of SARS-CoV-2 RNA on Urethral Swab in Patients with Positive Nasopharyngeal Swab

Background. The SARS-CoV-2 infection has caused one of the worst pandemics that history has ever known. SARS-CoV-2 can lead to multiple organ failure, which is life-threatening. Viral RNA is found in the lung, intestine, testicle, kidney, etc., which suggests the virus can be transmitted also via routes besides respiratory droplets. The aim of our study was to evaluate the presence of SARS-CoV-2 in urethral swabs. Methods. We enrolled ten patients with SARS-CoV-2 infection who attended the Infectious Diseases Unit of the A.O.U. Federico II of Naples, from March 2020 to April 2020. One urethral swab and one rhino-oropharyngeal swab were collected from each patient during SARS-CoV-2 infection. Results. All ten patients had a negative urethral swab for SARS-CoV-2 RNA, whereas the rhino-oropharyngeal swab was positive for SARS-CoV-2 RNA. This finding demonstrates that, in our patients, the virus did not affect the urinary tract and therefore would not be found in the urine, and even more importantly, it would not be transmitted via urine. This result was independent of the stage of the disease. Conclusion. If confirmed in larger studies, this observation could be the key to understanding the role of SARS-CoV-2 in relation to the genitourinary system.

HBV Core Promoter Inhibition by Tubulin Polymerization Inhibitor (SRI-32007)

Approximately 257 million people chronically infected with hepatitis B virus (HBV) worldwide are at risk of developing hepatocellular carcinoma (HCC). However, despite the availability of potent nucleoside/tide inhibitors, currently there are no curative therapies for chronic HBV infections. To identify potential new antiviral molecules, a select group of compounds previously evaluated in clinical studies were tested against 12 different viruses. Amongst the compounds tested, SRI-32007 (CYT997) demonstrated antiviral activity against HBV (genotype D) in HepG2.2.2.15 cell-based virus yield assay with 50% effective concentration (EC50) and selectivity index (SI) of 60.1 nM and 7.2, respectively. Anti-HBV activity of SRI-32007 was further confirmed against HBV genotype B in huh7 cells with secreted HBe antigen endpoint (EC50 40 nM and SI 250). To determine the stage of HBV life cycle inhibited by SRI-32007, time of addition experiment was conducted in HepG2-NTCP cell-based HBV infectious assay. Results indicated that SRI-32007 retained anti-HBV activity even when added 72 hours postinfection (72 h). Additional mechanism of action studies demonstrated potent inhibition of HBV core promoter activity by SRI-32007 with an EC50 of 40 nM and SI of >250. This study demonstrates anti-HBV activity of a repurposed compound SRI-32007 through inhibition of HBV core promoter activity. Further evaluation of SRI-32007 in HBV animal models is needed to confirm its activity in vivo. Our experiments illustrate the utility of repurposing strategy to identify novel antiviral chemical leads. HBV core promoter inhibitors such as SRI-32007 might enable the development of novel therapeutic strategies to combat HBV infections.

Human Papillomavirus Prevalence in Oral and Oropharyngeal Rinse and Gargle Specimens of Dental Patients and of an HIV-Positive Cohort from Pretoria, South Africa

Introduction. Studies on HPV prevalence in the head and neck region of South Africans are sparse. Of the available reports in the literature, there were no studies on the association between HPV-DNA presence in the mouth and oropharynx in relation to high-risk behaviours such as oral sex practice or tobacco and alcohol use. Materials and Methods. Following ethical clearance and informed consent, patients attending a regional HIV-management clinic and patients attending a dental hospital were recruited to this study. The participants completed an interview-based questionnaire obtaining demographic information, data on HIV serostatus, and behavioural data including sexual practices and tobacco and alcohol use, and a rinse-and-gargle specimen was taken. Specimens were analysed for HPV DNA on 3 separate PCR/qPCR platforms. Statistical analyses were performed for associations between the study group and categorical variables, HPV status, and data from the questionnaires. Results. Of 221 participants, 149 were from a general population and 72 from the HIV-management clinic. Smokers comprised 29.4% of the sample, and 45.2% of participants reported to have ever used alcohol. Open mouth kissing during teenage years was confirmed by 64.7% of participants, 40.3% have given oral sex with their mouth, and 44.8% confirmed to have received oral sex from their partner’s mouth. Seven participants (3.2%) had detectable α-HPV DNA, and 1 (0.4%) had detectable β-HPV DNA in their rinse-and-gargle specimens. Two participants were from the HIV-management clinic and 6 from the general dental population (overall 3.6%). Conclusion. Five high-risk HPV, 2 low-risk HPV, and one β-HPV types were detected. The low prevalence of 3.6% compares well to similar studies in different cohorts studied in South Africa and falls within the global oral/oropharyngeal prevalence spectrum. Only 4 participants, all from the HIV-management clinic, had palatine tonsils. No significant relationships were found between HPV presence and demographic data or sexual, oral sexual, tobacco use, or alcohol use, and no associations were seen with numbers of sexual and oral-sex partners.

Quadruple Therapy Offers High SVR Rates in Patients with HCV Genotype 4 with Previous Treatment Failure

Background and Aims. Direct-acting antivirals (DAAs) have made a revolution in hepatitis C virus (HCV) treatment with promising reduction of HCV infection and disease morbidities. However, unfortunately, treatment failure still occurs in about 5–15% of patients treated with DAA‐based combination regimens. The primary aim of the study was to assess the efficacy and safety of a quadruple regimen of (sofosbuvir, daclatasvir, and simeprevir with a weight-based ribavirin) in chronic HCV DAAs-experienced patients. Methods. This observational, open-label prospective study was carried out on 103 genotype 4 hepatitis C virus-infected patients who failed to achieve SVR12 after sofosbuvir-daclatasvir with or without ribavirin. Patients were treated for three months with sofosbuvir (400 mg), daclatasvir (60 mg), and simeprevir (150 mg) with a weight-based ribavirin dosage (1000–1200 mg/d). Response to treatment was determined by quantitative PCR for HCV at 3 months after the end of treatment (SVR12), and adverse events during the treatment were recorded. Results. SVR was achieved in 100 patients (97.1%) at week 12 after treatment. No dangerous or life-threatening adverse events were recorded. Conclusions. Retreatment of HCV genotype 4 patients with quadruple therapy is a good therapeutic option and achieves high response rates with minimal side effects.