Design of fluorinated sialic acid analog inhibitor to H5 hemagglutinin of H5N1 influenza virus through molecular dynamics simulation study

Influenza epidemics and pandemics are caused by influenza A virus. The cell surface protein of hemagglutinin and neuraminidase is responsible for viral infection and release of progeny virus on the host cell membrane. Now 18 hemagglutinin and 11 neuraminidase subtypes are identified. The avian influenza virus of H5N1 is an emergent threat to public health issues. To control the influenza viral infection it is necessary to develop antiviral inhibitors and vaccination. In the present investigation we carried out 50 ns Molecular Dynamics simulation on H5 hemagglutinin of Influenza A virus H5N1 complexed with fluorinated sialic acid by substituting fluorine atoms at any two hydroxyls of sialic acid by considering combinatorial combination. The binding affinity between the protein–ligand complex system is investigated by calculating pair interaction energy and MM-PBSA binding free energy. All the complex structures are stabilized by hydrogen bonding interactions between the H5 protein and the ligand fluorinated sialic acid. It is concluded from all the analyses that the fluorinated complexes enhance the inhibiting potency against H5 hemagglutinin and the order of inhibiting potency is SIA-F9 ≫ SIA-F2 ≈ SIA-F7 ≈ SIA-F2F4 ≈ SIA-F2F9 ≈ SIA-F7F9 > SIA-F7F8 ≈ SIA-F2F8 ≈ SIA-F8F9 > SIA-F4 ≈ SIA-F4F7 ≈ SIA-F4F8 ≈ SIA-F8 ≈ SIA-F2F7 ≈ SIA > SIA-F4F9. This study suggests that one can design the inhibitor by using the mono fluorinated models SIA-F9, SIA-F2 and SIA-F7 and difluorinated models SIA-F2F4, SIA-F2F9 and SIA-F7F9 to inhibit H5 of H5N1 to avoid Influenza A viral infection. Communicated by Ramaswamy H. Sarma</p

Viral infections in 47 CVID patients in allergy and immunology department of Rasool E Akram hospital in Tehran

Background: CVID is a heterogeneous primary immune deficiency with infectious, autoimmune and autoinflamatory features. It is most common symptomatic PID in Iran, with prevalence of 1 in 25000 to 50000 people. CVID has been divided into some phenotypes to produce more homogenized subpopulations. CVID is not a pure Ab deficiency .and because of both abnormalities in Tcell and innate immunity in combination with B cell dysfunction these patients are predisposed to viral and opportunistic infections. Method: prevalence of viral infections is reported in 47 CVID patients registered in Rasool E Akram hospital in Tehran. Patients have been diagnosed as CVID with the PAGID-ESID diagnostic criteria in our department or referred from other clinics for follow up and treatment. Diagnosis of viral germs has been made by clinical signs, pathological significances and in some cases by PCR. Cases: 9 patients (19%) had problems with viral infections. Infections occurred befor diagnosis of CVID in some cases or after that. Four patients (8.5 %) had problems with wart. Sever mucocutaneus HSV infection has occurred in 3 (6 %), recurrent zona in one (2 %) and CMV infection as colitis or pneumonitis in 3(6 %) patients. Sever progressive lethal CNS infection with JC virus occurred in one patient. Conclusion: evidences show that CVID is not a pure B cell defect, and we should be aware of opportunistic and viral infections that in some cases may be fatal