An Issue of Concern: Unique Truncated ORF8 Protein Variants of SARS-CoV-2

Open reading frame 8 (ORF8) protein is one of the most evolving accessory proteins in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19). It was previously reported that the ORF8 protein inhibits presentation of viral antigens by the major histocompatibility complex class I (MHC-I) and interacts with host factors involved in pulmonary inflammation. The ORF8 protein assists SARS-CoV-2 to evade immunity and replication. Among many contributing mutations, Q27STOP, a mutation in the ORF8 protein defines the B.1.1.7 lineage of SARS-CoV-2, which is engendering the second wave of COVID-19. In the present study, 47 unique truncated ORF8 proteins (T-ORF8) due to the Q27STOP mutations were identified among 49055 available B.1.1.7 SARS-CoV-2 sequences. The results show that only one of the 47 T-ORF8 variants spread to over 57 geo-locations in North America, and other continents which includes Africa, Asia, Europe and South America. Based on various quantitative features such as amino acid homology, polar/non-polar sequence homology, Shannon entropy conservation, and other physicochemical properties of all specific 47 T-ORF8 protein variants, a collection of nine possible T-ORF8 unique variants were defined. The question of whether T-ORF8 variants work similarly to ORF8 has yet to be investigated. A positive response to the question could exacerbate future COVID-19 waves, necessitating severe containment measures.

Variability of Accessory Proteins Rules the SARS-CoV-2 Pathogenicity

The coronavirus disease 2019 (COVID-19) is caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) which is pandemic with an estimated fatality rate less than 1% is ongoing. SARS-CoV-2 accessory proteins ORF3a, ORF6, ORF7a, ORF7b, ORF8, and ORF10 with putative functions to manipulate host immune mechanisms such as interferons, immune signaling receptor NLRP3 (NOD-, LRR-, and pyrin domain-containing 3) inflammasome, inflammatory cytokines such as interleukin 1{beta} (IL-1{beta}) are critical in COVID-19 pathology. Outspread variations of each of the six accessory proteins of all complete proteomes (available as of October 26, 2020, in the National Center for Biotechnology Information depository) of SARS-CoV-2, were observed across six continents. Across all continents, the decreasing order of percentage of unique variations in the accessory proteins was found to be ORF3a>ORF8>ORF7a>ORF6>ORF10>ORF7b. The highest and lowest unique variations of ORF3a were observed in South America and Oceania, respectively. This finding suggests that the wide variations of accessory proteins seem to govern the pathogenicity of SARS-CoV-2, and consequently, certain propositions and recommendations can be made in the public interest.

Possible transmission flow of SARS-CoV-2 based on ACE2 features

Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that is engendering the severe coronavirus disease 2019 (COVID-19) pandemic. The spike (S) protein receptor-binding domain (RBD) of SARS-CoV-2 binds to the three sub-domains viz. amino acids (aa) 22-42, aa 79-84, and aa 330-393 of ACE2 on human cells to initiate entry. It was reported earlier that the receptor utilization capacity of ACE2 proteins from different species, such as cats, chimpanzees, dogs, and cattle, are different. A comprehensive analysis of ACE2 receptors of nineteen species was carried out in this study, and the findings propose a possible SARS-CoV-2 transmission flow across these nineteen species.

Nano-Systems for Advanced Therapeutics and Diagnosis of Atherosclerosis.

Cardiovascular diseases (CVDs) are the leading cause of death and morbidity worldwide. Atherosclerotic situations such as acute myocardial infarction(MI) and stroke are still major causes of death worldwide. Present therapeutic approaches based on conventional drug delivery systems are not efficient to control these disorders. With the technological advancement and intervention of nanotechnology, several fascinating areas are explored for the management of these disorders. Targeted drug delivery approaches and diagnostic tools presented by nanotechnology, certainly took the atherosclerotic disease management to next level. Criticality lies in the rationale selection of an appropriately designed nanocarrier for targeting a specific zone of disease. Manuscript provides a descriptive view of disease targets; nanotechnology based therapeutic and diagnostic approaches and different nanocarriers to accomplish this task. It is important to have the understanding of different classes of these nanosystems along with their specific merits and demerits. Mechanisms and approaches for improving the selectivity or targeting potential are also discussed. There is no doubt that nanotechnology is having great impact in this area, but it is equally important to rationalize its scale up aspects for a real world success.

(Copper-curcumin) ß-cyclodextrin vaginal gel: delivering a novel metal-herbal approach for the development of topical contraception prophylaxis.

Delivering a safe and effective topical vaginal contraceptive is the need of present era. We explored the potential of a metal (copper) and herbal moiety (curcumin) for this topical contraceptive prophylaxis. Complex of copper and curcumin (Cu-Cur) was synthesized and the concerns regarding its aqueous solubility was resolved by including it into the hydrophobic cavity of ß-cyclodextrin (ß-CD) as (Cu-Cur)CD inclusion complex. Dose assessment was made on the basis of in-vitro spermicidal assays and cell cytotoxicity studies. Finally the (Cu-Cur)CD loaded vaginal gel was prepared, characterized and evaluated for in-vitro spermicidal activity and preclinical toxicity studies. Spectral and morphological characterizations confirmed the synthesis of (Cu-Cur) and (Cu-Cur)CD inclusion complex. Spermicidal assays and Hela cell cytotoxic data revealed an optimized 1.5% (Cu-Cur)CD for further studies. 1.5% w/w (Cu-Cur)CD loaded carbopol 974p gel provided 100% motility even at 2-fold dilution and preclinical toxicity studies in Rats and Rabbits revealed its highly safe profile. The hypothesis of considering metal-herbal complex and its cyclodextrin complex has worked and the well planned strategy of including it in (ß-CD) cavity provided a preeminent platform for vaginal delivery. In-vitro assays and preclinical toxicity analysis confirmed its potential to be used as highly safe and effective prophylaxis.

Intubating laryngeal mask airway as an independent ventilatory and intubation device. A comparison between supine, right lateral and left lateral / 대한마취과학회지

BACKGROUND: Sudden loss of airway in patients in the lateral position has always been proven to be difficult to manage with conventional laryngoscopy. We performed a randomized controlled trial to prove the success rate of ventilation and intubation in the lateral position via intubating laryngeal mask airway (ILMA). METHODS: Ninety patients were divided into three groups of 30 patients each, positioned supine, right lateral, and left lateral randomly. Each group comprised of both sexes of American Society of Anesthesiologists grade I and II, aged between 18-55 years with normal airway posted for surgery under general anesthesia. Patients were pre-medicated with fentanyl followed by induction with propofol and neuromuscular blockade with rocuronium. ILMA was inserted and blind tracheal intubation via ILMA was done. The success rate, time taken and the number of adjusting maneuvers used for both procedures were recorded. The data was tabulated and analyzed using ANOVA (analysis of variance), multiple 't' test and chi square. RESULTS: The success rate of intubation (96%) and time taken in insertion and intubation was found to be quite similar in all the three groups. CONCLUSIONS: We conclude that the ILMA has an important role to play in the emergency management of airways in patients in the lateral position in terms of ease, success rate and time taken.