SRSF protein kinases 1 and 2 are essential host factors for human coronaviruses including SARS-CoV-2

While vaccines are vital for preventing COVID-19 infections, it is critical to develop new therapies to treat patients who become infected. Pharmacological targeting of a host factor required for viral replication can suppress viral spread with a low probability of viral mutation leading to resistance. In particular, host kinases are highly druggable targets and a number of conserved coronavirus proteins, notably the nucleoprotein (N), require phosphorylation for full functionality. In order to understand how targeting kinases could be used to compromise viral replication, we used a combination of phosphoproteomics and bioinformatics as well as genetic and pharmacological kinase inhibition to define the enzymes important for SARS-CoV-2 N protein phosphorylation and viral replication. From these data, we propose a model whereby SRPK1/2 initiates phosphorylation of the N protein, which primes for further phosphorylation by GSK-3/{beta} and CK1 to achieve extensive phosphorylation of the N protein SR-rich domain. Importantly, we were able to leverage our data to identify an FDA-approved kinase inhibitor, Alectinib, that suppresses N phosphorylation by SRPK1/2 and limits SARS-CoV-2 replication. Together, these data suggest that repurposing or developing novel host-kinase directed therapies may be an efficacious strategy to prevent or treat COVID-19 and other coronavirus-mediated diseases.

Neuropathic Arthropathy Induced by Syringomyelia due to Arnold-Chiari I Malformation: A case report

Neuropathic arthropathy is a chronic and progressive disease of bone and joints. One of the most common causes of neuropathic arthropathy is syringomyelia. Syringomyelia associated with Arnold-Chiari I malformation has been well documented in many reports. We report a case of 76 year-old woman presented with the right elbow joint pain and stiffness. Her symptom was caused by neuropathic arthropathy associated with Arnold-Chiari I malformation and syringomyelia. The purpose of this paper is to emphasize that neuropathic arthropathy requires the evaluation of central nervous system to assess for occult causal lesion.

Nerve Conduction Study Findings and Risk Category of Diabetic Foot Screening Test

OBJECTIVE: To assess the correlation between the risk categories of diabetic foot screening test by 5.07 Semmes- Weinstein monofilament and the findings of standard nerve conduction studies of upper and lower extremities. METHOD: We studied 74 patients who were consulted to our department to rule out the diabetic neuropathy. We classified the patients to 4 risk groups by foot screening test using 5.07 Sememes-Weinstein monofilament, and performed the standard nerve conduction studies of upper and lower extremities. The risk categories of foot screening tests were compared to the findings of the nerve conduction studies. RESULTS: When the risk category becomes higher, there were more delay in latencies (motor and sensory potentials of median and ulnar nerve, sensory potentials of sural and superficial peroneal nerve, median and peroneal F-wave), slower conduction velocities (median, ulnar, peroneal, posterior tibial nerve) and lower amplitudes (motor and sensory potentials of media and ulnar nerve, peroneal and posterior tibial nerve, sural nerve) (p<0.05). Except for the amplitude of ulnar nerve and the latencies of peroneal and ulnar nerve, there were significant differences in the nerve conduction study data between the risk group 3 and the risk group 0 (p<0.05). CONCLUSION: We confirmed that the risk category of diabetic foot screening test by Semmes-Weinstein monofilament can meaningfully reflect the severity of diabetic neuropathy. We also suggest that it is necessary to pay attention to the nerve conduction study in the patients with history of foot ulcer.