Mutational landscape of SARS-CoV-2 genome in Turkey and impact of mutations on spike protein structure.

The Coronavirus Disease 2019 (COVID-19) was declared a pandemic in March 2020 by the World Health Organization (WHO). As of May 25th, 2021 there were 2.059.941 SARS-COV2 genome sequences that have been submitted to the GISAID database, with numerous variations. Here, we aim to analyze the SARS-CoV-2 genome data submitted to the GISAID database from Turkey and to determine the variant and clade distributions by the end of May 2021, in accordance with their appearance timeline. We compared these findings to USA, Europe, and Asia data as well. We have also evaluated the effects of spike protein variations, detected in a group of genome sequences of 13 patients who applied to our clinic, by using 3D modeling algorithms. For this purpose, we analyzed 4607 SARS-CoV-2 genome sequences submitted by different lab centers from Turkey to the GISAID database between March 2020 and May 2021. Described mutations were also introduced in silico to the spike protein structure to analyze their isolated impacts on the protein structure. The most abundant clade was GR followed by G, GH, and GRY and we did not detect any V clade. The most common variant was B.1, followed by B.1.1, and the UK variant, B.1.1.7. Our results clearly show a concordance between the variant distributions, the number of cases, and the timelines of different variant accumulations in Turkey. The 3D simulations indicate an increase in the surface hydrophilicity of the reference spike protein and the detected mutations. There was less surface hydrophilicity increase in the Asp614Gly mutation, which exhibits a more compact conformation around the ACE-2 receptor binding domain region, rendering the structure in a "down" conformation. Our genomic findings can help to model vaccination programs and protein modeling may lead to different approaches for COVID-19 treatment strategies.

IMPACT OF COVID-19 ON COMMERCIAL RELATIONS BETWEEN CHINA AND TURKEY

Amaç - Uluslararası ticareti ve ülke ekonomilerini derinden etkileyen COVID-19 ülkelerin getirdiǧi kısıtlamalar ile birlikte bir kriz haline dönüşmüştür. Bu baǧlamda, salgın döneminde Çin ve Türkiye arasındaki ikili ticari ilişkilerinin ve her iki ülkenin ekonomik durumu incelenerek özgün bir araştırma yapılması amaçlanmaktadır. Yöntem - Araştırmada nitel ve nicel veri toplama yöntemleri uygulanmıştır. Bulgular - Araştırma bulgularında, 2020 Aralık ayında geçen senenin aynı ayına kıyasla, Türkiye'nin Çin'e ihracatı %15,70, Çin'den ithalatı ise %32,16 bir artış görülmüştür. Her iki ülkeyi ayrı deǧerlendirdiǧimizde elde edilen sonuçlar, 2020'de Türkiye'nin ihracatı %6,3 düşüş gösterirken, ithalatı ise %4,3 artmıştır. 2020 Aralık'ta 2019'un Aralıka kıyasla Çin'in ihracatı 18,1% artarken, ithalatı ise %6,5 oranında artışla rekor seviyeye ulaşmıştır. Sonuç - Her iki ülkenin ticari ilişkileri her ne kadar istenilen düzeyde olmasa da salgın döneminde pozitif yönde gelişme kaydetmiştir.Alternate abstract:Purpose - COVID-19, which deeply affects international trade and national economies, has turned into a crisis with the restrictions imposed by countries. During the pandemic, it is aimed to make an original research by examining bilateral commercial relations between China and Turkey and the situation of each both country's economy. Methodology - Qualitative and quantitative data collection methods were used in the study. Findings - It seen the increase at 15.70% in exports by Turkey to China and 32.16% in imports from China in 2020 Dec compared with the same month in 2019. Turkey's exports have decreased 6.3%, while its imports increased 4.3% in 2020. In 2020 Dec compared with 2019 Dec, Chinese exports increased by 18.1%, while its imports reached a record level, with an increase of 6.5%. Conclusions - Although the commercial relations of both countries were not at the desired level, they were shown positive improvement during the pandemic period.

Gamma-irradiated SARS-CoV-2 vaccine candidate, OZG-38.61.3, confers protection from SARS-CoV-2 challenge in human ACEII-transgenic mice.

The SARS-CoV-2 virus caused the most severe pandemic around the world, and vaccine development for urgent use became a crucial issue. Inactivated virus formulated vaccines such as Hepatitis A and smallpox proved to be reliable approaches for immunization for prolonged periods. In this study, a gamma-irradiated inactivated virus vaccine does not require an extra purification process, unlike the chemically inactivated vaccines. Hence, the novelty of our vaccine candidate (OZG-38.61.3) is that it is a non-adjuvant added, gamma-irradiated, and intradermally applied inactive viral vaccine. Efficiency and safety dose (either 1013 or 1014 viral RNA copy per dose) of OZG-38.61.3 was initially determined in BALB/c mice. This was followed by testing the immunogenicity and protective efficacy of the vaccine. Human ACE2-encoding transgenic mice were immunized and then infected with the SARS-CoV-2 virus for the challenge test. This study shows that vaccinated mice have lowered SARS-CoV-2 viral RNA copy numbers both in oropharyngeal specimens and in the histological analysis of the lung tissues along with humoral and cellular immune responses, including the neutralizing antibodies similar to those shown in BALB/c mice without substantial toxicity. Subsequently, plans are being made for the commencement of Phase 1 clinical trial of the OZG-38.61.3 vaccine for the COVID-19 pandemic.

Preclinical efficacy and safety analysis of gamma-irradiated inactivated SARS-CoV-2 vaccine candidates.

COVID-19 outbreak caused by SARS-CoV-2 created an unprecedented health crisis since there is no vaccine for this novel virus. Therefore, SARS-CoV-2 vaccines have become crucial for reducing morbidity and mortality. In this study, in vitro and in vivo safety and efficacy analyzes of lyophilized vaccine candidates inactivated by gamma-irradiation were performed. The candidate vaccines in this study were OZG-3861 version 1 (V1), an inactivated SARS-CoV-2 virus vaccine, and SK-01 version 1 (V1), a GM-CSF adjuvant added vaccine. The candidate vaccines were applied intradermally to BALB/c mice to assess toxicity and immunogenicity. Preliminary results in vaccinated mice are reported in this study. Especially, the vaccine models containing GM-CSF caused significant antibody production with neutralization capacity in absence of the antibody-dependent enhancement feature, when considered in terms of T and B cell responses. Another important finding was that the presence of adjuvant was more important in T cell in comparison with B cell response. Vaccinated mice showed T cell response upon restimulation with whole inactivated SARS-CoV-2 or peptide pool. This study shows that the vaccines are effective and leads us to start the challenge test to investigate the gamma-irradiated inactivated vaccine candidates for infective SARS-CoV-2 virus in humanized ACE2 + mice.