Dissecting the intricacies of human antibody responses to SARS-CoV-1 and SARS-CoV-2 infection.

The 2003 severe acute respiratory syndrome coronavirus (SARS-CoV-1) causes more severe disease than SARS-CoV-2, which is responsible for COVID-19. However, our understanding of antibody response to SARS-CoV-1 infection remains incomplete. Herein, we studied the antibody responses in 25 SARS-CoV-1 convalescent patients. Plasma neutralization was higher and lasted longer in SARS-CoV-1 patients than in severe SARS-CoV-2 patients. Among 77 monoclonal antibodies (mAbs) isolated, 60 targeted the receptor-binding domain (RBD) and formed 7 groups (RBD-1 to RBD-7) based on their distinct binding and structural profiles. Notably, RBD-7 antibodies bound to a unique RBD region interfaced with the N-terminal domain of the neighboring protomer (NTD proximal) and were more prevalent in SARS-CoV-1 patients. Broadly neutralizing antibodies for SARS-CoV-1, SARS-CoV-2, and bat and pangolin coronaviruses were also identified. These results provide further insights into the antibody response to SARS-CoV-1 and inform the design of more effective strategies against diverse human and animal coronaviruses.

Identification, characterization and expression analysis of circRNA encoded by SARS-CoV-1 and SARS-CoV-2.

Virus-encoded circular RNA (circRNA) participates in the immune response to viral infection, affects the human immune system, and can be used as a target for precision therapy and tumor biomarker. The coronaviruses SARS-CoV-1 and SARS-CoV-2 (SARS-CoV-1/2) that have emerged in recent years are highly contagious and have high mortality rates. In coronaviruses, little is known about the circRNA encoded by the SARS-CoV-1/2. Therefore, this study explores whether SARS-CoV-1/2 encodes circRNA and characteristics and functions of circRNA. Based on RNA-seq data of SARS-CoV-1 and SARS-CoV-2 infections, we used circRNA identification tools (circRNA_finder, find_circ and CIRI2) to identify circRNAs. The number of circRNAs encoded by SARS-CoV-1 and SARS-CoV-2 was identified as 151 and 470, respectively. It can be found that SARS-CoV-2 shows more prominent circRNA encoding ability than SARS-CoV-1. Expression analysis showed that only a few circRNAs encoded by SARS-CoV-1/2 showed high expression levels, and the positive strand produced more abundant circRNAs. Then, based on the identified SARS-CoV-1/2-encoded circRNAs, we performed circRNA identification and characterization using the previously developed CirRNAPL. Finally, target gene prediction and functional enrichment analysis were performed. It was found that viral circRNA is closely related to cancer and has a potential role in regulating host cell functions. This study studied the characteristics and functions of viral circRNA encoded by coronavirus SARS-CoV-1/2, providing a valuable resource for further research on the function and molecular mechanism of coronavirus circRNA.

Discovery of Nanosota-2, -3, and -4 as super potent and broad-spectrum therapeutic nanobody candidates against COVID-19.

IMPORTANCE: The COVID-19 pandemic exposed limitations of conventional antibodies as therapeutics, including high cost, limited potency, ineffectiveness against new viral variants, and primary reliance on injection-only delivery. Nanobodies are single-domain antibodies with therapeutic potentials. We discovered three anti-SARS-CoV-2 nanobodies, named Nanosota-2, -3, and -4, from an immunized alpaca. Nanosota-2 is super potent against prototypic SARS-CoV-2, Nanosota-3 is highly potent against the omicron variant, and Nanosota-4 is effective against both SARS-CoV-1 and SARS-CoV-2. In addition to their super potency and combined broad antiviral spectrum, these nanobodies are cost-effective, can be easily adapted to new viral variants through phage display, and can potentially be administered as inhalers. The Nanosota series are powerful therapeutic candidates to combat circulating SARS-CoV-2 and prepare for possible future coronavirus pandemics.

Assessing the inhibitory effects of some secondary amines, thioureas and 1,3-dimethyluracil conjugates of (-)-cytisine and thermopsine on the RNA-dependent RNA polymerase of SARS-CoV-1 and SARS-CoV-2.

SARS-CoV-2 causes COVID-19, with symptoms ranging from mild to severe, including pneumonia and death. This beta coronavirus has a 30-kilobase RNA genome and shares about 80 % of its nucleotide sequence with SARS-CoV-1. The replication/transcription complex, essential for viral RNA synthesis, includes RNA-dependent RNA polymerase (RdRp, nsp12) enhanced by nsp7 and nsp8. Antivirals like molnupiravir and remdesivir, which are RdRp inhibitors, treat severe COVID-19 but have limitations, highlighting the need for new therapies. This study assessed (-)-cytisine, methylcytisine, and thermopsine derivatives against SARS-CoV-1 and SARS-CoV-2 in vitro, focusing on their RdRp inhibition. Selected compounds from a previous study were evaluated using a SARS-CoV-2 RNA polymerase assay kit to investigate their structure-activity relationships. Compound 17 (1,3-dimethyluracil conjugate with (-)-cytisine and thermopsine) emerged as a potent inhibitor of SARS-CoV-1 and SARS-CoV-2 RdRp, with an IC50 value of 7.8 µM against SARS-CoV-2 RdRp. It showed a dose-dependent reduction in cytopathic effects in cells infected with SARS-CoV-1 and SARS-CoV-2 replicon-based single-round infectious particles (SRIPs) and significantly inhibited SARS-CoV N protein expression, with EC50 values of 0.12 µM for SARS-CoV-1 and 1.47 µM for SARS-CoV-2 SRIPs. Additionally, compound 17 reduced viral subgenomic RNA levels in a concentration-dependent manner in SRIP-infected cells. The structure-activity relationships of compound 17 with SARS-CoV-1 and SARS-CoV-2 RdRp were also investigated, highlighting it as a promising lead for developing antiviral agents against SARS and COVID-19.

The SARS-CoV-2 spike S1 protein induces global proteomic changes in ATII-like rat L2 cells that are attenuated by hyaluronan.

The COVID-19 pandemic continues to impose a major impact on global health and economy since its identification in early 2020, causing significant morbidity and mortality worldwide. Caused by the SARS-CoV-2 virus, along with a growing number of variants, COVID-19 has led to 651,918,402 confirmed cases and 6,656,601 deaths worldwide (as of December 27, 2022; https://covid19.who.int/). Despite advances in our understanding of COVID-19 pathogenesis, the precise mechanism by which SARS-CoV2 causes epithelial injury is incompletely understood. In this current study, robust application of global-discovery proteomics identified highly significant induced changes by the Spike S1 protein of SARS-CoV-2 in the proteome of alveolar type II (ATII)-like rat L2 cells that lack ACE2 receptors. Systems biology analysis revealed that the S1-induced proteomics changes were associated with three significant network hubs: E2F1, CREB1/RelA, and ROCK2/RhoA. We also found that pretreatment of L2 cells with high molecular weight hyaluronan (HMW-HA) greatly attenuated the S1 effects on the proteome. Western blotting analysis and cell cycle measurements confirmed the S1 upregulation of E2F1 and ROCK2/RhoA in L2 cells and the protective effects of HMW-HA. Taken as a whole, our studies revealed profound and novel biological changes that contribute to our current understanding of both S1 and hyaluronan biology. These data show that the S1 protein may contribute to epithelial injury induced by SARS-CoV-2. In addition, our work supports the potential benefit of HMW-HA in ameliorating SARS CoV-2-induced cell injury.

Characterization of cross-reactive monoclonal antibodies against SARS-CoV-1 and SARS-CoV-2: Implication for rational design and development of pan-sarbecovirus vaccines and neutralizing antibodies.

Emergence of various circulating SARS-CoV-2 variants of concern (VOCs) promotes the identification of pan-sarbecovirus vaccines and broadly neutralizing antibodies (bNAbs). Here, to characterize monoclonal antibodies cross-reactive against both SARS-CoV-1 and SARS-CoV-2 and to search the criterion for bNAbs against all emerging SARS-CoV-2, we isolated several SARS-CoV-1-cross-reactive monoclonal antibodies (mAbs) from a wildtype SARS-CoV-2 convalescent donor. These antibodies showed broad binding capacity and cross-neutralizing potency against various SARS-CoV-2 VOCs, including B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), and B.1.617.2 (Delta), but failed to efficiently neutralize Omicron variant and its sublineages. Structural analysis revealed how Omicron sublineages, but not other VOCs, efficiently evade an antibody family cross-reactive against SARS-CoV-1 through their escape mutations. Further evaluation of a series of SARS-CoV-1/2-cross-reactive bNAbs showed a negative correlation between the neutralizing activities against SARS-CoV-1 and SARS-CoV-2 Omicron variant. Together, these results suggest the necessity of using cross-neutralization against SARS-CoV-1 and SARS-CoV-2 Omicron as criteria for rational design and development of potent pan-sarbecovirus vaccines and bNAbs.

Reduced neutralization and Fc effector function to Omicron subvariants in sera from SARS-CoV-1 survivors after two doses of CoronaVac plus one dose subunit vaccine.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron harbors more than 30 mutations of the spike protein and exhibits substantial immune evasion. Although previous study indicated that BNT162b2 messenger RNA vaccine induces potent cross-clade pan-sarbecovirus neutralizing antibodies in survivors of the infection by SARS-CoV-1, the neutralization activity and Fc-mediated effector functions of these cross-reactive antibodies elicited in SARS-CoV-1 survivors to Omicron subvariants still remain largely unknown. In this study, the neutralization activity and Fc-mediated effector functions of antibodies boosted by a third dose vaccination were characterized in SARS-CoV-1 convalescents and healthy individuals. Potent cross-clade broadly neutralizing antibodies were observed in SARS-CoV-1 survivors who received a three-dose vaccination regimen consisting of two priming doses of CoronaVac followed by one booster dose of the protein subunit vaccine ZF2001. However, the induced antibodies exhibited both reduced neutralization and impaired Fc effector functions targeting multiple Omicron subvariants. Importantly, the data also support the notion that immune imprints resulted from SARS-CoV-1 infection may exacerbate the impairment of neutralization activity and Fc-mediated effector functions to Omicron subvariants and provided invaluable information to vaccination strategy in future.

Comparative analysis of inflight transmission of SARS-CoV-2, influenza, and SARS-CoV-1.

The aim of this study is to evaluate the infection risk of aircraft passengers seated within and beyond two rows of the index case(s) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A(H1N1)pdm09 virus, and SARS-CoV-1. PubMed databases were searched for articles containing information on air travel-related transmission of SARS-CoV-2, influenza A(H1N1)pdm09 virus, and SARS-CoV-1 infections. We performed a meta-analysis of inflight infection data. In the eight flights where the attack rate could be calculated, the inflight SARS-CoV-2 attack rates ranged from 2.6% to 16.1%. The risk ratios of infection for passengers seated within and outside the two rows of the index cases were 5.64 (95% confidence interval (CI):1.94-16.40) in SARS-CoV-2 outbreaks, 4.26 (95% CI:1.08-16.81) in the influenza A(H1N1)pdm09 virus outbreaks, and 1.91 (95% CI:0.80-4.55) in SARS-CoV-1 outbreaks. Furthermore, we found no significant difference between the attack rates of SARS-CoV-2 in flights where the passengers were wearing masks and those where they were not (p = 0.22). The spatial distribution of inflight SARS-CoV-2 outbreaks was more similar to that of the influenza A(H1N1)pdm09 virus outbreaks than to that of SARS-CoV-1. Given the high proportion of asymptomatic or pre-symptomatic infection in SARS-CoV-2 transmission, we hypothesised that the proximity transmission, especially short-range airborne route, might play an important role in the inflight SARS-CoV-2 transmission.

Coronavirus Inhibitors Targeting nsp16.

During the past three decades, humans have been confronted with different new coronavirus outbreaks. Since the end of the year 2019, COVID-19 threatens the world as a rapidly spreading infectious disease. For this work, we targeted the non-structural protein 16 (nsp16) as a key protein of SARS-CoV-2, SARS-CoV-1 and MERS-CoV to develop broad-spectrum inhibitors of nsp16. Computational methods were used to filter candidates from a natural product-based library of 224,205 compounds obtained from the ZINC database. The binding of the candidates to nsp16 was assessed using virtual screening with VINA LC, and molecular docking with AutoDock 4.2.6. The top 9 compounds were bound to the nsp16 protein of SARS-CoV-2, SARS-CoV-1, and MERS-CoV with the lowest binding energies (LBEs) in the range of -9.0 to -13.0 kcal with VINA LC. The AutoDock-based LBEs for nsp16 of SARS-CoV-2 ranged from -11.42 to -16.11 kcal/mol with predicted inhibition constants (pKi) from 0.002 to 4.51 nM, the natural substrate S-adenosyl methionine (SAM) was used as control. In silico results were verified by microscale thermophoresis as in vitro assay. The candidates were investigated further for their cytotoxicity in normal MRC-5 lung fibroblasts to determine their therapeutic indices. Here, the IC50 values of all three compounds were >10 µM. In summary, we identified three novel SARS-CoV-2 inhibitors, two of which showed broad-spectrum activity to nsp16 in SARS-CoV-2, SARS-CoV-1, and MERS-CoV. All three compounds are coumarin derivatives that contain chromen-2-one in their scaffolds.

Antibody and T-cellular response to COVID-19 booster vaccine in SARS-CoV-1 survivors.

The severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) survivors are more likely to produce a potent immune response to SARS-CoV-2 after booster vaccination. We assessed humoral and T cell responses against SARS-CoV-2 in previously vaccinated SARS-CoV-1 survivors and naïve healthy individuals (NHIs) after a booster Ad5-nCoV dose. Boosted SARS-CoV-1 survivors had a high neutralization of SARS-CoV-2 Wuhan-Hu-1 (WA1), Beta, and Delta but is limited to Omicron subvariants (BA.1, BA.2, BA.2.12.1, and BA.4/BA.5). Most boosted SARS-CoV-1 survivors had robust SARS-CoV-2-specific CD4+ and CD8+ T cell responses. While booster vaccination in NHIs elicited less or ineffective neutralization of WA1, Beta, and Delta, and none of them induced neutralizing antibodies against Omicron subvariants. However, they developed comparable SARS-CoV-2-specific T cell responses compared to boosted SARS-CoV-1 survivors. These findings suggest that boosted Ad5-nCoV would not elicit effective neutralizing antibodies against Omicron subvariants in SARS-CoV-1 survivors and NHIs but induced comparable robust T cell responses. Achieving a high antibody titer in SARS-CoV-1 survivors and NHIs is desirable to generate broad neutralization.

Mapping molecular gene signatures mediated by SARS-COV-2 and large-scale and genome-wide transcriptomics comparative analysis among respiratory viruses of medical importance.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging RNA virus causing COVID-19 disease, across the globe. SARS-CoV-2 infected patients may exhibit acute respiratory distress syndrome which can be compounded by endemic respiratory viruses and thus highlighting the need to understand the genetic bases of clinical outcome under multiple respiratory infections. In this study, 42 individual datasets and a multi-parametric based selected list of over 12,000 genes against five medically important respiratory viruses (SARS-CoV-2, SARS-CoV-1, influenza A, respiratory syncytial virus (RSV) and rhinovirus were collected and analysed in an attempt to understand differentially regulated gene patterns and to cast genetic markers of individual and multiple co-infections. While a certain cohort of virus-specific genes were regulated (negatively and positively), notably results revealed a greatest correlation among genes regulation by SARS-CoV-2 and RSV. Furthermore, out of analysed genes, the MAP2K5 and NFKBIL1 were specifically and highly upregulated in SARS-CoV-2 infection both in vivo or in vitro. The most conserved genetic signature was JAK2 gene as well as the constitutively downregulated ZNF219 gene. In contrast, several genes including GPBAR1 and SC5DL were specifically downregulated in SARS-CoV-2 datasets. Finally, we catalogued a set of genes that were conserved or differentially regulated across studied respiratory viruses. These finding provide foundational and genome-wide data to gauge the markers of respiratory viral infections individually and under co-infection. This work compares the virogenomic signatures among human respiratory viruses and provides valid targets for potential antiviral therapy.

Ferrets are valuable models for SARS-CoV-2 research.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulted in an ongoing pandemic with millions of deaths worldwide. Infection of humans can be asymptomatic or result in fever, fatigue, dry cough, dyspnea, and acute respiratory distress syndrome with multiorgan failure in severe cases. The pathogenesis of COVID-19 is not fully understood, and various models employing different species are currently applied. Ferrets can be infected with SARS-CoV-2 and efficiently transmit the virus to contact animals. In contrast to hamsters, ferrets usually show mild disease and viral replication restricted to the upper airways. Most reports have used the intranasal inoculation route, while the intratracheal infection model is not well characterized. Herein, we present clinical, virological, and pathological data from young ferrets intratracheally inoculated with SARS-CoV-2. Infected animals showed no significant clinical signs, and had transient infection with peak viral RNA loads at 4 days postinfection, mild to moderate rhinitis, and pulmonary endothelialitis/vasculitis. Viral antigen was exclusively found in the respiratory epithelium of the nasal cavity, indicating a particular tropism for cells in this location. Viral antigen was associated with epithelial damage and influx of inflammatory cells, including activated neutrophils releasing neutrophil extracellular traps. Scanning electron microscopy of the nasal respiratory mucosa revealed loss of cilia, shedding, and rupture of epithelial cells. The currently established ferret SARS-CoV-2 infection models are comparatively discussed with SARS-CoV-2 pathogenesis in mink, and the advantages and disadvantages of both species as research models for zoonotic betacoronaviruses are highlighted.

The effectiveness of hand hygiene interventions for preventing community transmission or acquisition of novel coronavirus or influenza infections: a systematic review.

BACKGROUND: Novel coronaviruses and influenza can cause infection, epidemics, and pandemics. Improving hand hygiene (HH) of the general public is recommended for preventing these infections. This systematic review examined the effectiveness of HH interventions for preventing transmission or acquisition of such infections in the community. METHODS: PubMed, MEDLINE, CINAHL and Web of Science databases were searched (January 2002-February 2022) for empirical studies related to HH in the general public and to the acquisition or transmission of novel coronavirus infections or influenza. Studies on healthcare staff, and with outcomes of compliance or absenteeism were excluded. Study selection, data extraction and quality assessment, using the Cochrane Effective Practice and Organization of Care risk of bias criteria or Joanna Briggs Institute Critical Appraisal checklists, were conducted by one reviewer, and double-checked by another. For intervention studies, effect estimates were calculated while the remaining studies were synthesised narratively. The protocol was pre-registered (PROSPERO 2020: CRD42020196525). RESULTS: Twenty-two studies were included. Six were intervention studies evaluating the effectiveness of HH education and provision of products, or hand washing against influenza. Only two school-based interventions showed a significant protective effect (OR: 0.64; 95% CI 0.51, 0.80 and OR: 0.40; 95% CI 0.22, 0.71), with risk of bias being high (n = 1) and unclear (n = 1). Of the 16 non-intervention studies, 13 reported the protective effect of HH against influenza, SARS or COVID-19 (P < 0.05), but risk of bias was high (n = 7), unclear (n = 5) or low (n = 1). However, evidence in relation to when, and how frequently HH should be performed was inconsistent. CONCLUSIONS: To our knowledge, this is the first systematic review of effectiveness of HH for prevention of community transmission or acquisition of respiratory viruses that have caused epidemics or pandemics, including SARS-CoV-1, SARS-CoV-2 and influenza viruses. The evidence supporting the protective effect of HH was heterogeneous and limited by methodological quality; thus, insufficient to recommend changes to current HH guidelines. Future work is required to identify in what circumstances, how frequently and what product should be used when performing HH in the community and to develop effective interventions for promoting these specific behaviours in communities during epidemics.

An overview of solutions for airborne viral transmission reduction related to HVAC systems including liquid desiccant air-scrubbing.

The spread of the coronavirus SARS-CoV-2 affects the health of people and the economy worldwide. As air transmits the virus, heating, ventilation and air-conditioning (HVAC) systems in buildings, enclosed spaces and public transport play a significant role in limiting the transmission of airborne pathogens at the expenses of increased energy consumption and possibly reduced thermal comfort. On the other hand, liquid desiccant technology could be adopted as an air scrubber to increase indoor air quality and inactivate pathogens through temperature and humidity control, making them less favourable to the growth, proliferation and infectivity of microorganisms. The objectives of this study are to review the role of HVAC in airborne viral transmission, estimate its energy penalty associated with the adoption of HVAC for transmission reduction and understand the potential of liquid desiccant technology. Factors affecting the inactivation of pathogens by liquid desiccant solutions and possible modifications to increase their heat and mass transfer and sanitising characteristics are also described, followed by an economic evaluation. It is concluded that the liquid desiccant technology could be beneficial in buildings (requiring humidity control or moisture removal in particular when viruses are likely to present) or in high-footfall enclosed spaces (during virus outbreaks).

Effectiveness of SARS-CoV-2 Vaccines for Short- and Long-Term Immunity: A General Overview for the Pandemic Contrast.

BACKGROUND: The recent COVID-19 pandemic produced a significant increase in cases and an emergency state was induced worldwide. The current knowledge about the COVID-19 disease concerning diagnoses, patient tracking, the treatment protocol, and vaccines provides a consistent contribution for the primary prevention of the viral infection and decreasing the severity of the SARS-CoV-2 disease. The aim of the present investigation was to produce a general overview about the current findings for the COVID-19 disease, SARS-CoV-2 interaction mechanisms with the host, therapies and vaccines' immunization findings. METHODS: A literature overview was produced in order to evaluate the state-of-art in SARS-CoV-2 diagnoses, prognoses, therapies, and prevention. RESULTS: Concerning to the interaction mechanisms with the host, the virus binds to target with its Spike proteins on its surface and uses it as an anchor. The Spike protein targets the ACE2 cell receptor and enters into the cells by using a special enzyme (TMPRSS2). Once the virion is quietly accommodated, it releases its RNA. Proteins and RNA are used in the Golgi apparatus to produce more viruses that are released. Concerning the therapies, different protocols have been developed in observance of the disease severity and comorbidity with a consistent reduction in the mortality rate. Currently, different vaccines are currently in phase IV but a remarkable difference in efficiency has been detected concerning the more recent SARS-CoV-2 variants. CONCLUSIONS: Among the many questions in this pandemic state, the one that recurs most is knowing why some people become more seriously ill than others who instead contract the infection as if it was a trivial flu. More studies are necessary to investigate the efficiency of the treatment protocols and vaccines for the more recent detected SARS-CoV-2 variant.

[Increased LAMP1 Expression Enhances SARS-CoV-1 and SARS-CoV-2 Production in Vero-Derived Transgenic Cell Lines].

Coronaviridae is a family of single-stranded RNA (ssRNA) viruses that can cause diseases with high mortality rates. SARS-CoV-1 and MERS-CoV appeared in 2002-2003 and 2012, respectively. A novel coronavirus, SARS-CoV-2, emerged in 2019 in Wuhan (China) and has caused more than 5 million deaths in worldwide. The entry of SARS-CoV-1 into the cell is due to the interaction of the viral spike (S) protein and the cell protein, angiotensin-converting enzyme 2 (ACE2). After infection, virus assembly occurs in Golgi apparatus-derived vesicles during exocytosis. One of the possible participants in this process is LAMP1 protein. We established transgenic Vero cell lines with increased expression of human LAMP1 gene and evaluated SARS-CoV-1 and SARS-CoV-2 production. An increase in the production of both viruses in LAMP1-expressing cells when compared with Vero cells was observed, especially in the presence of trypsin during infection. From these results it can be assumed that LAMP1 promotes SARS-CoV-1 and SARS-CoV-2 production due to enhanced exocytosis.

Beta coronaviruses and human endocrine system: new data (review of literature).

A new dangerous respiratory disease COVID-19 was first reported in China in December 2019, the pathogen SARS-Coronavirus 2 (SARS-CoV-2), belonging to the beta coronavirus genus, which, in addition to SARS-CoV-2, includes SARS-CoV-1 and MERS-CoV. The genome of SARS-CoV-2 is almost 80% similar to SARS-CoV-1 and 50% to MERS-CoV. The mechanisms of infection of SARS-CoV-1 and SARS-CoV-2 are also similar and occur through the binding of the virus to the type 2 angiotensin-converting enzyme protein (ACE2), which is widely represented in the human body with predominant expression in endocrine tissues. In this connection, SARS-CoV-1 and SARS-CoV-2 affect the organs of the endocrine system, causing damage and hormonal changes that affect the prognosis of the course of COVID-19. This literature review is devoted to the analysis of changes in the organs of the endocrine system that occur during infection with SARS-CoV-1 and SARS-CoV-2, as well as the potential effect of hormones on susceptibility to SARS-CoV-2.

The recent outbreaks of human coronaviruses: A medicinal chemistry perspective.

Coronaviruses (CoVs) infect both humans and animals. In humans, CoVs can cause respiratory, kidney, heart, brain, and intestinal infections that can range from mild to lethal. Since the start of the 21st century, three ß-coronaviruses have crossed the species barrier to infect humans: severe-acute respiratory syndrome (SARS)-CoV-1, Middle East respiratory syndrome (MERS)-CoV, and SARS-CoV-2 (2019-nCoV). These viruses are dangerous and can easily be transmitted from human to human. Therefore, the development of anticoronaviral therapies is urgently needed. However, to date, no approved vaccines or drugs against CoV infections are available. In this review, we focus on the medicinal chemistry efforts toward the development of antiviral agents against SARS-CoV-1, MERS-CoV, SARS-CoV-2, targeting biochemical events important for viral replication and its life cycle. These targets include the spike glycoprotein and its host-receptors for viral entry, proteases that are essential for cleaving polyproteins to produce functional proteins, and RNA-dependent RNA polymerase for viral RNA replication.

Knee osteonecrosis after COVID-19.

BACKGROUND: COVID-19 is an emergent infection, the long-term complications of which are still under study. While hypercoagulability is a common feature in severe cases, the incidence of ischemic complications such as osteonecrosis remains unknown. Previous studies on SARS-CoV1 found an increase in osteonecrosis 3-36 months after infection, and it is still unclear if this was related to the use of corticosteroids or to the virus itself. METHODS: We introduce a 78-year-old woman who complained of right knee pain and swelling a month after COVID-19 infection onset. Her knee radiography showed no significant changes compared to previous ones. MRI, on the other hand, found osteonecrosis in the internal femoral condyle. No coagulation abnormalities were found in blood tests. RESULTS: While knee replacement should be her main treatment, it will be long delayed due to the pandemic. In the meantime, we increased her tapentadol and salicylic acid doses and gave her home exercises to improve functionality. CONCLUSION: In the follow-up after COVID-19, any muscular or joint pain with unusual characteristics should be carefully examined.

Coronavirus: Pure Infectious Disease or Genetic Predisposition.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes novel coronavirus disease (COVID-19), is the seventh pathogenic coronavirus recently discovered in December 2019 in Wuhan, China. To date, our knowledge about its effect on the human host remains limited. It is well known that host genetic factors account for the individual differences in the susceptibility to infectious diseases. The genetic susceptibility factors to COVID-19 and its severity are associated with several unanswered questions. However, the experience gained from an earlier strain of coronavirus, SARS-CoV-1, which shows 78% genetic similarity to SARS-CoV-2 and uses the same receptor to bind to host cells, could provide some clues. It, therefore, seems possible to assemble new evidence in order to solve a potential genetic predisposition puzzle for COVID-19. In this chapter, the puzzle pieces, including virus entry receptors, immune response, and inflammation-related genes, as well as the probable genetic predisposition models to COVID-19, are discussed.