The SARS-CoV-2 spike protein is vulnerable to moderate electric fields.

Most of the ongoing projects aimed at the development of specific therapies and vaccines against COVID-19 use the SARS-CoV-2 spike (S) protein as the main target. The binding of the spike protein with the ACE2 receptor (ACE2) of the host cell constitutes the first and key step for virus entry. During this process, the receptor binding domain (RBD) of the S protein plays an essential role, since it contains the receptor binding motif (RBM), responsible for the docking to the receptor. So far, mostly biochemical methods are being tested in order to prevent binding of the virus to ACE2. Here we show, with the help of atomistic simulations, that external electric fields of easily achievable and moderate strengths can dramatically destabilise the S protein, inducing long-lasting structural damage. One striking field-induced conformational change occurs at the level of the recognition loop L3 of the RBD where two parallel beta sheets, believed to be responsible for a high affinity to ACE2, undergo a change into an unstructured coil, which exhibits almost no binding possibilities to the ACE2 receptor. We also show that these severe structural changes upon electric-field application also occur in the mutant RBDs corresponding to the variants of concern (VOC) B.1.1.7 (UK), B.1.351 (South Africa) and P.1 (Brazil). Remarkably, while the structural flexibility of S allows the virus to improve its probability of entering the cell, it is also the origin of the surprising vulnerability of S upon application of electric fields of strengths at least two orders of magnitude smaller than those required for damaging most proteins. Our findings suggest the existence of a clean physical method to weaken the SARS-CoV-2 virus without further biochemical processing. Moreover, the effect could be used for infection prevention purposes and also to develop technologies for in-vitro structural manipulation of S. Since the method is largely unspecific, it can be suitable for application to other mutations in S, to other proteins of SARS-CoV-2 and in general to membrane proteins of other virus types.

[Effect of treatment in loss of retinal nerve fibre layer in multiple sclerosis patients]. / Influencia del tratamiento en la pérdida de fibras nerviosas de la retina en pacientes con esclerosis múltiple.

OBJECTIVE: To evaluate the effect of pathogenic treatments in the reduction of the retinal nerve fibre layer (RNFL) in patients with Multiple Sclerosis (MS) by means of ocular imaging technologies. MATERIAL AND METHODS: A total 155 eyes of 79 patients with MS were enrolled in this study. All patients underwent a complete ophthalmic examination including best corrected visual acuity using Snellen chart, colour vision using Ishihara pseudoisochromatic plates, visual field examination, optical coherence tomography (OCT), scanning laser polarimetry (GDx) and visual evoked potentials. The patients were re-evaluated after a one year period and changes were assessed in order to detect differences between treatments using the Anova statistical test. The patients were divided into four groups: 1) Patients without treatment, 2) Patients treated with interferon beta-1a, 3) Subjects who received interferon beta-1b, 4) Patients treated using glatiramer acetate. RESULTS: There were no statistically significant differences between patients with or without treatment and between the four groups (P>0.05, t test), but functional and structural parameters showed greater loss in RNFL thickness in non-treated patients. Temporal quadrant RNFL thickness measured by OCT was the parameter with the highest variation (reduction of 4.97µm in patients without treatment vs 1.08µm in treated patients). CONCLUSIONS: MS pathogenic treatment may be a protective factor in the RNFL loss that is associated to the disease progression. More studies are needed.