Background: By 27 June 2020, almost half a million people had died due to COVID-19 infections. The susceptibility and severity of infection vary significantly across nations. The contribution of chronic viral and parasitic infections to immune homeostasis remains a concern. By investigating the role of interferon (IFN)-γ, we conducted this study to understand the connection between the decrease in numbers and severity of COVID-19 cases within parasitic endemic regions. Our research included 375 patients referred to hospitals for diagnosis of COVID-19 infection. Patients were subjected to full investigations, in particular severe acute respiratory syndrome coronavirus-2 nucleic acid and Toxoplasma IgM and IgG antibody detection, stool examination, and quantitative IFN-γ measurement. Results: The majority of the studied cases had chest manifestation either alone (54.7%) or in association with gastrointestinal (GIT) manifestations (19.7%), whereas 25.6% had GIT symptoms. We reported parasitic infections in 72.8% of mild COVID-19 cases and 20.7% of severe cases. Toxoplasma gondii, Cryptosporidium, Blastocyst, and Giardia were the most common parasitic infections among the COVID-19 cases studied. Conclusion: The remarkable adaptation of human immune response to COVID-19 infection by parasitic infections with high levels of IFN-γ was observed in moderate cases compared with low levels in extreme cases. The potential therapeutic efforts aimed at the role of parasitic infection in immune system modulation are needed if this hypothesis is confirmed.

According to the World Health Organization (WHO), SARS-CoV-2 is responsible for more than 5 M deaths and is reported in 223 countries infecting 250+ M people. Despite the current vaccination momentum, thousands of people die every day by COVID-19. Suggesting possible blockers of the viral RNA-dependent RNA polymerase is highly needed for potential effective therapeutics against SARS-CoV-2. This study utilizes combined molecular dynamics simulation and molecular docking to test novel guanosine derivatives against SARS-CoV-2 RdRp. Results reveal the binding potency of nineteen guanosine derivatives against SARS-CoV-2 solved structures. The bulky moieties (hydroxyl or fluorated phenyl moieties) added to the 2′ position of the ribose ring positively impacted the binding affinity to RdRp. The current in silico study represents a one-step-ahead for suggesting new possible blockers of SARS-CoV-2 RdRp that are yet to be verified in the wet lab. It offers new potential binders or blockers of RdRp that bind to the protein active site tighter than remdesivir. The latter was approved by the food and drug administration (FDA) for emergency use against COVID-19 last year.

Human cytomegalovirus (HCMV) is the most common cause of severe morbidity and mortality in immune- compromised individuals. This study was conducted to determine the incidence of HCMV infection in HCV patients who either spontaneously cleared the virus or progressed to chronic HCV infection. The study included a total of eighty four cases (48 females and 36 males) that were referred to blood banks for blood donation with an age range of 18-64 years (mean age 37.62 ± 10.03 years). Hepatitis C virus RNA and HCMV DNA were detected in sera by RT-nested PCR and nested PCR respectively in all subjects. Immunoglobulin G levels for HCV and HCMV were determined. Besides, IgM antibodies for HCMV infection were also determined in subjects' sera. Fifty three out of 84 cases (63%) were positive for HCV-RNA while 31 (37%) cases had negative HCV RNA. Forty six (87%) and 13 (25%) cases out of 53 HCV RNA positive patients were positive for HCMV IgG and IgM antibodies respectively. While 20 of 53 cases (38%) had detectable HCMV DNA. To examine the role of HCMV infection in HCV spontaneous resolution, two groups of HCV patients, group 1) chronic HCV infection (positive HCV RNA and positive IgG antibodies) vs group 2) spontaneous resolution (negative HCV RNA and positive IgG antibodies) were compared. The percentages of positive CMV IgG and IgM results is higher in chronic HCV patient than those in spontaneously cleared HCV patients and the difference is highly statistically significant (P value < 0.001). Also, there is a general trend towards elevated levels of CMV IgG antibodies in HCV chronic patients than those in spontaneously cleared HCV patients (P value < 0.02). HCMV DNA detection in group 1 was more than twice the value observed in group 2 (38% vs 14.3%, P value < 0.001). Moreover, levels of liver enzymes were significantly higher in HCV RNA positive cases co-infected with HCMV DNA than HCMV negative cases (P value < 0.001). The results indicate the role of HCMV in the liver pathogenesis. We conclude that chronic HCV patients co-infected with HCMV infection can be regarded as high risk groups for liver disease progression where they should be monitored for the long term outcome of the disease.

Host–virus relationships regulate every phase of viral infection and critically influence course of illness and the effectiveness of treatment. Viruses utilize host receptors, intracellular trafficking routes, metabolic programs, and immunological signaling networks to introduce infection, while host cells use innate and adaptive immune responses that both limit viral replication and, in certain situations, cause tissue damage. Given the fast viral evolution and drug resistance linked to virus-directed therapy, there is growing proof that these host-dependent mechanisms are appealing and underutilized targets for antiviral treatment. Recent developments in single-cell technology, proteomics, and functional genomics have made it possible to systematically identify host dependency and restriction factors shared by different viral families, exposing common molecular vulnerabilities that might be targeted therapeutically. This review integrates current knowledge of virus–host interplay via a translational lens, highlighting processes that directly guide the formation of host-directed antivirals and immune-regulating treatments. We emphasize host processes involved in viral entry, replication, and immune signaling that have shown therapeutic significance, while illustrating the difficulties of balancing antiviral effectiveness with immunopathology. By framing host–virus interactions through a therapeutic lens, this review attempts to offer a targeted and translationally relevant viewpoint for next-generation antiviral research.